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SmI2–H2O-Mediated 5-exo/6-exo Lactone
Radical Cyclisation Cascades
Irem Yalavac,† Sarah E. Lyons,
† Michael R. Webb,
‡ and David J. Procter
†*
†School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, UK
‡Medicines Research Centre, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Herts, SG1
2NY, UK
Supplementary Information
General Methods ...................................................................................................................... 2
Experimental Protocols and Characterisation Data ............................................................. 3
Crystal data and Structure Refinements ............................................................................. 41
Figure S1 Crystal Structure of 2b (CCDC 1009956) ............................................... 41
Table S1 Crystal data and structure refinement for 2b (CCDC 1009956) ............ 41
Figure S2 Crystal Structure of 2d (CCDC 1012766) ............................................... 43
Table S2 Crystal data and structure refinement for 2d (CCDC 1012766) ............ 43
References ............................................................................................................................... 45
1H and
13C NMR spectra ....................................................................................................... 46
Corresponding Author:
Professor David J. Procter
School of Chemistry, University of Manchester
Oxford Road
Manchester, M13 9PL, United Kingdom
Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2014
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S2
General Methods
1H-NMR and
13C-NMR spectra were recorded on Bruker NMR spectrometers (400 MHz and
500 MHz for 1H-NMR, 100 MHz and 125 MHz for
13C-NMR).
1H-NMR chemical shifts (δH)
and 13
C-NMR chemical shifts (δC) are quoted in parts per million (ppm) downfield from
trimethylsilane (TMS) and coupling constants (J) are quoted in Hertz (Hz). Abbreveations
for NMR data are s (singlet), d (doublet), t (triplet), q (quartet), quin (quintet), sxt (sextet).
Infrared (IR) spectra were recorded on a Bruker Alpha FTIR spectrometer and mass spectra
were recorded on a Micromass Platform II (ESI), Agilent 5975C Triple Axis GCMS (GC-
MS, EI/CI) and Waters QTOF (HRMS). 1H-NMR and
13C-NMR spectra were assigned with
the aid of COSY, HSQC, HMBC and DEPT 90/135 NMR techniques and stereochemistry
assigned with the aid of X-ray crystallography. Flash column chromatography was carried
out using Sigma Aldrich silica gel 60 Angstrom (Ǻ), 240 – 400 mesh. Thin layer
chromatography (TLC) was performed on aluminium sheets pre-coated with silica gel, 0.20
mm (Macherey-Nagel, Polygram® Sil G/UV254). TLC plates were visualised by UV
absorption, phosphomolybdic acid, vanillin or potassium permanganate solution and heating.
Diiodoethane was washed with diethyl ether and sodium thiosulfate before use.
Tetrahydrofuran (THF) was pre-dried over sodium wire and distilled from sodium
benzophenone ketyl prior to use. Diisopropylamine (DIPA) and dichloromethane (DCM)
were both distilled from calcium hydride prior to use.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S3
Experimental Protocols and Characterisation Data
Preparation of SmI21
An oven-dried flask equipped with a dry stirrer bar was flushed with a strong flow of N2 for
30 minutes and loaded with samarium metal (-40 mesh, 1.4 equiv.) and washed diiodoethane
(1 equiv.). The flask was flushed for another 30 minutes, after which freshly distilled and
degassed THF (0.1 M) was added under stirring. Using an exit needle and a gentle flow of N2
for the first 5-10 minutes allowed for any ethene gas formed in-situ to evacuate the reaction
vessel. Stirring was continued under a positive pressure of N2 overnight at room temperature.
Before titration, the mixture was allowed to settle for one hour and used straight away.
Ethyl 4-(2-methyl-1,3-dioxolan-2-yl)butanoate – S12
To a stirred solution of ethyl 5-oxohexanoate (2.00 mL, 12.6 mmol, 1 equiv.) and ethylene
glycol (2.50 mL, 44.3 mmol, 3.5 equiv.) in benzene (18 mL) was added p-toluenesulfonic
acid monohydrate (48.0 mg, 0.25 mmol, 0.02 equiv.) and the mixture was heated to reflux for
21 hours using Dean-Stark conditions. The solvent was removed in vacuo and purification by
flash column chromatography (5% EtOAc:hexane) yielded the named compound as a
colourless oil (1.95 g, 77%); δH (400 MHz, CDCl3) 1.26 (3H, t, J 7.1, CO2CH2CH3), 1.33
(3H, s, CH3), 1.61 – 1.79 (4H, m, 2 × CH2), 2.33 (2H, t, J 7.1, CH2), 3.89 – 3.99 (4H, m, 2 ×
OCH2), 4.13 (2H, q, J 7.2, CO2CH2CH3); δC (100 MHz, CDCl3) 14.2 (CH2CH3), 19.6 (CH2),
23.8 (CH3), 34.3 (CH2), 38.3 (CH2), 60.2 (CH2CH3), 64.6 (-OCH2CH2O-), 109.8 (C-
OCH2CH2O-), 173.5 (CO2Et).
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S4
General Procedure A: Alkylation of protected keto-esters
Ethyl 2-(2-(2-methyl-1,3-dioxolan-2-yl)ethyl)hept-6-enoate – S2
An oven-dried flask was degassed with N2 and n-BuLi (5.00 mL, 7.89 mmol, 1.1 equiv., 1.6
M in hexane) was added slowly to a mixture of DIPA (1.10 mL, 7.89 mmol, 1.1 equiv.) and
THF (4.5 mL) at -78 °C. After stirring the solution for 1 hour at -78 °C, ethyl 4-(2-methyl-
1,3-dioxolan-2-yl)butanoate (1.45 g, 7.17 mmol, 1 equiv.) in THF (2.8 mL) was added over
30 minutes using a syringe pump. Stirring was continued for 45 minutes and 5-bromo-1-
pentene (1.15 mL, 9.75 mmol, 1.36 equiv.) in HMPA (1.5 mL) was added to the mixture,
which was allowed to warm to room temperature and stirred overnight. The reaction was
quenched with an aqueous saturated solution of NH4Cl (20 mL). After separation, the
aqueous layer was extracted with EtOAc (3 × 20 mL). The organic layers were combined and
washed with brine (20 mL), dried over Na2SO4 and concentrated in vacuo. Flash column
chromatography (5% EtOAc:hexane) yielded the named compound as a yellow oil (1.20 g,
62%); υmax / cm-1
3078, 2978, 2934, 2862, 1718, 1641, 1446, 1367, 1156, 1027, 911; δH (400
MHz, CDCl3) 1.22 (3H, t, J 7.6, CO2CH2CH3), 1.26 (3H, s, CH3), 1.31 – 1.38 (2H, m, CH2),
1.39 – 1.71 (6H, m, 3 × CH2), 1.97 – 2.05 (2H, m, C=CHCH2), 2.24 – 2.33 (1H, m, CH), 3.83
– 3.93 (4H, m, 2 × OCH2), 4.1 (2H, qd, J 7.3, 1.3, CO2CH2CH3), 4.87 – 5.00 (2H, m,
C=CHCH2), 5.67 – 5.79 (1H, m, C=CHCH2); δC (100 MHz, CDCl3) 14.2 (CH2CH3), 23.6
(CH3), 26.5 (CH2), 26.6 (CH2), 31.7 (CH2), 33.5 (CH2), 36.5 (CH2), 45.3 (CH), 60.0
(CH2CH3), 64.5 (-OCH2CH2O-), 64.5 (-OCH2CH2O-), 109.6 (C-OCH2CH2O-), 114.6
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S5
(CH=CH2), 138.3 (CH=CH2), 175.9 (CO2Et); m/z (ESI+) 294 ([M + Na]+, 100%); HRMS
(ESI+) found 271.1898, expect 271.1904 for C15H27O4.
General Procedure B: Deprotection of alkylated keto-esters
Ethyl 2-(3-oxobutyl)hept-6-enoate – S3
A mixture of ethyl 2-(2-(2-methyl-1,3-dioxolan-2-yl)ethyl)hept-6-enoate (0.60 g, 2.22 mmol,
1 equiv.), p-toluenesulfonic acid monohydrate (0.84 g, 4.44 mmol, 2 equiv.) and acetone (25
mL) was stirred at room temperature for 2 hours. After quenching with an aqueous saturated
solution of NaHCO3 (20 mL), the aqueous layer was extracted with CH2Cl2 (3 × 15 mL). The
organic layers were combined and dried over Na2SO4 and the crude compound was
concentrated in vacuo. The title compound was obtained by flash column chromatography
(5% EtOAc:hexane) as a colourless oil (0.48 g, 96%); υmax / cm-1
2935, 1720, 1367, 1158; δH
(400 MHz, CDCl3) 1.26 (3H, t, J 7.2, CO2CH2CH3), 1.33 – 1.52 (3H, m, 1H from CH2 +
CH2), 1.58 – 1.69 (1H, m, 1H from CH2), 1.81 (2H, q, J 7.5, CH2), 2.05 (2H, q, J 6.8,
C=CHCH2), 2.13 (3H, s, CH3), 2.29 – 2.38 (1H, m, CH), 2.44 (2H, td, J 7.6, 3.0, COCH2),
4.14 (2H, q, J 6.8, CO2CH2CH3), 4.92 – 5.04 (2H, m, HC=CH2), 5.71 – 5.84 (1H, m,
HC=CH2); δC (100 MHz, CDCl3) 14.3 (CH2CH3), 25.9 (CH2), 26.5 (CH2), 30.0 (CH2), 31.8
(CH3), 33.5 (CH2), 41.1 (CH2), 44.6 (CH), 60.3 (CH2CH3), 114.7 (CH=CH2), 138.3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S6
(CH=CH2), 175.7 (CO2Et), 208.0 (CO); m/z (ESI+) 249 ([M + Na]+, 100%); HRMS (ESI+)
found 249.1450, expect 249.1461 for C13H22O3Na.
General Procedure C: Appel reaction
(3-Bromoprop-1-yn-1-yl)benzene – S42
To a stirred mixture of 3-phenyl-2-propyn-1-ol (1.00 g, 7.57 mmol, 1 equiv.) in CH2Cl2 (25
mL) was added CBr4 (3.01 g, 9.09 mmol, 1.2 equiv.) and the mixture was cooled to 0 °C.
PPh3 (2.38 g, 9.09 mmol, 1.2 equiv.) was added in 3 portions and the reaction was stirred
under N2 at room temperature for 3 hours. The solvent was removed in vacuo and inorganic
residues were removed by filtration through silica gel (hexane → 1% EtOAc:hexane). The
crude product was taken through to the next step; δH (500 MHz, CDCl3) 4.18 (2H, s, CH2Br),
7.3 – 7.4 (3H, m, ArCH), 7.42 – 7.52 (2H, m, ArCH); δC (125 MHz, CDCl3) 15.3 (CH2), 84.2
(C≡C), 86.7 (C≡C), 122.1 (ArC), 128.3 (ArCH), 128.9 (ArCH), 131.9 (ArCH).
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S7
General Procedure D: Barbier-type lactonization reaction
rac-(3R,6S)-6-Methyl-3-(pent-4-en-1-yl)-6-(1-phenylpropa-1,2-dien-1-yl)tetrahydro-2H-
pyran-2-one – trans-1a and rac-(3S,6S)-6-ethyl-3-(pent-4-en-1-yl)-6-(1-phenylpropa-1,2-
dien-1-yl)tetrahydro-2H-pyran-2-one – cis-1a
An oven-dried flask was degassed with N2 and loaded with NiI2 (8 mg, 0.027 mmol, 2 mol%
with respect to SmI2) and SmI2 (17.0 mL, 1.33 mmol, 3 equiv.) and the mixture was cooled to
0 °C. Immediately after the addition of ethyl 2-(3-oxobutyl)hept-6-enoate (100 mg, 0.44
mmol, 1 equiv.) to the stirring mixture, (3-bromoprop-1-yn-1-yl)benzene (112 mg, 0.57
mmol, 1.3 equiv.) in THF (4.4 mL) was added dropwise over 30 minutes. Once warmed up to
room temperature, the reaction was opened to air and stirred until decolourisation occurred.
The reaction was quenched with Rochelle’s salt (10 mL) and extracted from Et2O (3 × 15
mL). The organic layers were washed with brine (20 mL) and dried over Na2SO4. The solvent
was removed in vacuo and flash column chromatography (5% EtOAc:hexane) yielded trans-
1a and cis-1a as a yellow oil (28 mg, 21% each, combined yield 42%).
For trans-1a: υmax / cm-1
3075, 2931, 2860, 1773, 1728, 1445, 1216, 1073, 907, 853, 765, 700;
δH (400 MHz, CDCl3) 1.42 - 1.54 (3H, m, 1H from CH2 + CH2), 1.61 (3H, s, CH3), 1.62 -
1.69 (1H, m, 1H from CH2), 1.83 - 1.87 (1H, m, 1H from CH2), 1.88 - 1.96 (1H, m, 1H from
CH2), 2.04 - 2.15 (3H, m, 1H from CH2 + CH2), 2.23 (1H, ddd, J 14.1, 7.6, 6.3, 1H from
CH2), 2.38 - 2.45 (1H, m, CH), 4.93 - 5.06 (2H, m, HC=CH2), 5.11 (2H, s, C=CH2), 5.80
(1H, ddt, J 17.1, 10.2, 6.7, HC=CH2), 7.25 - 7.29 (1H, m, ArH), 7.30 - 7.37 (2H, m, ArH),
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S8
7.41 - 7.47 (2H, m, ArH); δC (100 MHz, CDCl3) 22.6 (CH2), 26.1 (CH2), 28.1 (CH3), 30.9
(CH2), 31.8 (CH2), 33.6 (CH2), 38.6 (CH), 78.6 (C=CH2), 82.9 (quat. C), 110.3 (C=C=CH2),
114.7 (CH=CH2), 127.5 (ArCH), 128.4 (ArCH), 129.0 (ArCH), 134.1 (ArC), 138.4
(CH=CH2), 174.0 (CO), 207.4 (C=CH2); m/z (ESI+) 319 ([M + Na]+, 100%); HRMS (ESI+)
found 319.1661, expect 319.1669 for C20H24O2Na.
For cis-1a: υmax / cm-1
3075, 2930, 2861, 1726, 1447, 1223, 1135, 1093, 911, 763, 700; δH
(500 MHz, CDCl3) 1.28 - 1.45 (3H, m, 1H from CH2 + CH2), 1.51 - 1.53 (3H, s, CH3), 1.63 -
1.78 (2H, m, 1H from CH2 + 1H from CH2), 1.78 - 1.91 (2H, m, 1H from CH2 + 1H from
CH2), 1.94 - 2.05 (2H, m, CH2), 2.12 - 2.18 (1H, m, 1H from CH2), 2.28 - 2.37 (1H, m, CH),
4.85 - 5.03 (4H, m, HC=CH2 + C=CH2), 5.67 - 5.77 (1H, m, HC=CH2), 7.18 - 7.30 (5H, m,
ArH); δC (125 MHz, CDCl3) 22.9 (CH2), 26.0 (CH2), 28.7 (CH3), 31.2 (CH2), 32.4 (CH2),
33.7 (CH2), 39.8 (CH), 78.7 (C=CH2), 83.3 (quat. C), 110.6 (C=C=CH2), 114.8 (CH=CH2),
127.6 (ArCH), 128.4 (ArCH), 129.1 (ArCH), 134.7 (ArC), 138.4 (CH=CH2), 173.5 (CO),
207.1 (C=CH2); m/z (ESI+) 297.3 ([M + H]+, 100%); HRMS (ESI+) found 297.1861, expect
297.1849 for C20H25O2.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S9
General Procedure E: Cascade Cyclisation
(4S,4aS,5S,6S,7R,9aS)-4,5,7-Trimethyl-6-phenyldecahydro-4aH-benzo[7]annulene-4a,7-
diol 2a and (1S,2R,3R,4S,5R)-1,3-dimethyl-5-(pent-4-en-1-yl)-2-phenylcycloheptane-1,4-
diol 3a
An oven-dried flask was degassed with N2 and loaded with distilled H2O (2.88 mL, 0.16 mol,
4000 equiv.) and rac-(3R,6S)-6-methyl-3-(pent-4-en-1-yl)-6-(1-phenylpropa-1,2-dien-1-
yl)tetrahydro-2H-pyran-2-one trans-1a (12.0 mg, 0.04 mmol, 1 equiv.) in THF (0.4 mL) and
the mixture was stirred at room temperature for 5 minutes. SmI2 (6.40 mL, 0.62 mmol, 16
equiv.) was added over 30 minutes and the reaction mixture was stirred at room temperature
under a positive pressure of N2 in a sealed flask until decolourisation occurred (48 h). The
flask was opened to air and the reaction was quenched with Rochelle’s salt (3 mL) and
extracted from Et2O (3 × 5 mL). The organic layers were combined and washed with brine
(10 mL) and dried over Na2SO4. Flash column chromatography (10% EtOAc:hexane → 20%
EtOAc:hexane) yielded 3a (4 mg, 33%) and 2a (1.2 mg, 10%) as a colourless oil.
For 2a: υmax / cm-1
3423, 2925, 1450, 1375, 1143, 914, 702; δH (400 MHz, CDCl3) 0.73 (3H,
d, J 6.8, CH3), 1.07 (3H, s, CH3), 1.16 - 1.28 (2H, m, CH2), 1.29 - 1.35 (5H, m, 1H from CH2
+ 1H from CH2 + CH3), 1.37 - 1.54 (4H, m, 1H from CH2 + CH2 + CH), 1.56 - 1.72 (2H, m,
1H from CH2 + CHCH3), 1.80 (1H, dd, J 15.2, 11.7, 1H from CH2), 1.96 - 2.05 (1H, m, 1H
from CH2), 2.21 (1H, q, J 7.8, CHCH3), 3.89 (1H, s, CHPh), 7.21 - 7.29 (1H, m, ArH), 7.29 -
7.35 (2H, m, ArH), 7.37 - 7.41 (2H, m, ArH); δC (100 MHz, CDCl3) 13.3 (CH3), 14.6 (CH3),
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S10
26.0 (CH2), 26.3 (CH2), 28.2 (CH3), 30.8 (2 × CH2), 37.4 (CH), 43.2 (CH2), 43.6 (CHMe),
45.0 (CH), 49.3 (CHPh), 74.8 (quat. C), 76.8 (quat. C), 126.2 (ArCH), 128.3 (ArCH), 129.6
(ArCH), 145.4 (ArC); m/z (ESI-) 301 ([M - H]-, 100%); m/z (ESI+) 267.3 ([M –H2O -
-OH]
+,
100%); HRMS (ESI+) found 325.2151, expect 325.2144 for C20H30O2Na.
For 3a: δH (500 MHz, CDCl3) 0.98 (3H, s, CH3), 1.15 - 1.22 (1H, m, 1H from CH2), 1.24
(3H, d, J 7.3, CH3), 1.27 - 1.41 (1H, m, 1H from CH2), 1.42 - 1.68 (5H, m, 1H from CH2 +
1H from CH2 + CH2 + CH), 1.85 - 1.94 (2H, m, CH2), 1.94 - 2.06 (2H, m, CH2), 2.38 - 2.46
(1H, m, CHCH3), 2.85 (1H, s, CHPh), 3.37 (1H, dd, J 9.1, 4.3, CHOH), 4.85 - 4.99 (2H, m,
HC=CH2), 5.69 - 5.83 (1H, m, HC=CH2), 7.14 - 7.20 (1H, m, ArH), 7.21 - 7.31 (4H, m,
ArH); δC (125 MHz, CDCl3) 13.8 (CH3), 24.3 (CH2), 26.0 (CH2), 29.3 (CH3), 29.7 (CH2),
34.0 (CH2), 34.2 (CH2), 42.2 (CH2), 44.3 (CH), 56.5 (CHPh), 74.2 (quat. C), 80.7 (CHOH),
114.4 (CH=CH2), 126.6 (ArCH), 128.3 (ArCH), 129.6 (ArCH), 139.0 (CH=CH2), 139.6
(ArC); m/z (ESI+) 325.3 ([M + Na]+, 100%); m/z (ESI+) 267.3 ([M – H2O - OH]
+, 100%).
General Procedure F: Cross-metathesis
(E)-Ethyl 2-(3-oxobutyl)-7-phenylhept-6-enoate – S5
As described in general procedure F, stirring ethyl 2-(3-oxobutyl)hept-6-enoate (0.58 g, 2.55
mmol, 1 equiv.), styrene (0.88 mL, 7.65 mmol, 3 equiv.) and Grubbs’ catalyst second
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S11
generation (22 mg, 25.5 µmol, 1 mol%) in CH2Cl2 (6 mL) overnight at reflux with
subsequent work-up and purification by flash column chromatography (toluene → 2%
EtOAc:toluene) yielded the named compound as a colourless oil (0.52 g, 67%); υmax / cm-1
3025, 2934, 1717, 1447, 1367, 1154, 1026, 965, 734, 693; δH (400 MHz, CDCl3) 1.27 (3H, t,
J 7.3, CH2CH3), 1.42 – 1.57 (3H, m, 1 H from CH2 + CH2), 1.64 – 1.75 (1H, m, 1H from
CH2), 1.82 (2H, q, J 7.5, CH2), 2.13 (3H, s, CH3), 2.21 (2H, q, J 6.8, CH2), 2.31 – 2.41 (1H,
m, CH), 2.45 (2H, td, J 7.4, 2.8, CH2), 4.15 (2H, q, J 7.1, CH2CH3), 6.16 (1H, dt, J 15.8, 6.8,
CH2CH=CH), 6.38 (1H, d, J 15.9, CH2CH=CH), 7.2 (1H, tt, J 7.1, 1.5, ArH), 7.27 – 7.34
(4H, m, ArH); δC (100 MHz, CDCl3) 14.3 (CH2CH3), 25.9 (CH2), 26.9 (CH2), 30.0 (CH3),
31.9 (CH2), 32.8 (CH2), 41.1 (CH2), 44.6 (CH), 60.3 (CH2CH3), 125.9 (ArCH), 126.9
(ArCH), 128.4 (ArCH), 130.2 (CH2CH=CH and CH2CH=CH), 137.7 (ArC), 175.7 (CO2Et),
208.0 (CO); m/z (ESI+) 325 ([M + Na]+, 100%); HRMS (ESI+) found 320.2214, expect
320.2220 for C19H30O3N.
rac-(3R,6S)-6-Methyl-3-((E)-5-phenylpent-4-en-1-yl)-6-(1-phenylpropa-1,2-dien-1-
yl)tetrahydro-2H-pyran-2-one – trans-1b
As described in general procedure D, reaction of (E)-ethyl 2-(3-oxobutyl)-7-phenylhept-6-
enoate (0.25 g, 0.33 mmol, 1 equiv.), (3-bromoprop-1-yn-1-yl)benzene (0.20 g, 1.08 mmol,
1.3 equiv.), SmI2 (33.0 mL, 2.69 mmol, 4 equiv.) and NiI2 (20.0 mg, 0.06 mmol, 2 mol %
with respect to SmI2), after work-up and flash column chromatography (5% EtOAc:hexane)
yielded trans-1b as a yellow oil (combined yield for cis and trans isomers: 24%, for trans-
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S12
1b: 37 mg, 12%); υmax / cm-1
3025, 2450, 1728, 1493, 1448, 1216, 1092, 1074, 965, 765, 697;
δH (500 MHz, CDCl3) 1.51 - 1.59 (3H, m, 1H from CH2 + CH2), 1.61 (3H, s, CH3), 1.64 -
1.71 (1H, m, 1H from CH2), 1.86 (1H, quin, J 6.7, 1H from CH2), 1.93 - 2.01 (1H, m, 1H
from CH2), 2.12 (1H, sxt, J 6.9, 1H from CH2), 2.19 - 2.29 (3H, m, 1H from CH2 + CH2),
2.40 - 2.48 (1H, m, CH), 5.11 (2H, s, C=CH2), 6.21 (1H, dt, J 15.8, 6.9, CH2CH=CH), 6.39
(1H, d, J 15.8, CH2CH=CH), 7.17 - 7.23 (1H, m, ArH), 7.26 - 7.38 (7H, m, ArH), 7.43 - 7.47
(2H, m, ArH); δC (125 MHz, CDCl3) 22.7 (CH2), 26.7 (CH2), 28.1 (CH3), 31.0 (CH2), 31.9
(CH2), 32.9 (CH2), 38.6 (CH), 78.7 (C=CH2), 82.9 (quat. C), 110.3 (C=C=CH2), 125.9
(ArCH), 126.9 (ArCH), 127.5 (ArCH), 128.4 (ArCH), 128.5 (ArCH), 129.0 (ArCH), 130.2
(CH2CH=CH and CH2CH=CH), 134.1 (ArC), 137.7 (ArC), 174.0 (CO), 207.4 (C=CH2); m/z
(ESI+) 395.2 ([M + Na]+, 100%); HRMS (ESI+) found 395.1996, expect 395.1982 for
C26H28O2Na.
rac-(4R,4aR,5S,6S,7R,9aS)-4-Benzyl-5,7-dimethyl-6-phenyldecahydro-1H-
benzo[7]annulene-4a,7-diol – 2b and (1S,2R,3R,4S,5R)-1,3-dimethyl-2-phenyl-5-((E)-5-
phenylpent-4-en-1-yl)cycloheptane-1,4-diol – 4b
As described in general procedure E, reaction of rac-(3R,6S)-6-methyl-3-((E)-5-phenylpent-
4-en-1-yl)-6-(1-phenylpropa-1,2-dien-1-yl)tetrahydro-2H-pyran-2-one trans-1b (35.0 mg,
0.09 mmol, 1 equiv.), H2O (6.80 mL, 0.38 mol, 4000 equiv.) and SmI2 (14.0 mL, 1.50 mmol,
16 equiv.), after work-up and flash column chromatography (10% EtOAc:hexane → 20%
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S13
EtOAc:hexane) yielded 4b (3 mg, 8%) and 2b (13 mg, 37%) as a colourless oil and a white
solid, respectively.
For 2b: m. p. 149 – 153 °C (MeOH); υmax / cm-1
3472, 2933, 1718, 1610, 1454, 1369, 755,
699; δH (500 MHz, CDCl3) 1.11 (3H, s, CH3), 1.13 - 1.19 (2H, m, 1H from CH2 + 1H from
CH2), 1.20 - 1.26 (1H, m, 1H from CH2), 1.31 - 1.38 (1H, m, 1H from CH2), 1.41 - 1.50 (5H,
m, CH2 + CH3), 1.52 - 1.65 (2H, m, 1H from CH2 + CH), 1.73 - 1.81 (1H, m, CH), 1.85 (1H,
dd, J 15.3, 11.8, 1H from CH2), 1.99 - 2.13 (3H, m, 1H from CH2Ph + CH2), 2.52 (1H, q, J
7.9, CHCH3), 2.87 (1H, dd, J 13.4, 3.3, 1H from CH2Ph), 3.93 (1H, s, CHPh), 7.05 - 7.09
(2H, m, ArH), 7.14 - 7.18 (1H, m, ArH), 7.22 - 7.26 (3H, m, ArH), 7.31 - 7.35 (2H, m, ArH),
7.40 - 7.44 (2H, m, ArH); δC (125 MHz, CDCl3) 13.3 (CH3) 25.8 (CH2), 26.4 (CH2), 26.6
(CH2), 28.3 (CH3), 30.9 (CH2), 34.7 (CH2), 43.0 (CHMe), 43.1 (CH2), 44.4 (CH), 45.2 (CH),
49.4 (CHPh), 74.7 (quat. C), 77.2 (quat. C), 125.7 (ArCH), 126.3 (ArCH), 128.2 (ArCH),
128.3 (ArCH), 129.1 (ArCH), 129.6 (ArCH), 141.3 (ArC), 145.3 (ArC); HRMS (ESI+) found
401.2473, expect 401.2457 for C26H34O2Na.
For 4b: δH (500 MHz, CDCl3) 0.89 (3H, d, J 6.9, CH3), 0.95 (3H, s, CH3), 1.48 - 1.67 (4H, m,
CH2 + CH2), 1.74 - 1.80 (1H, m, 1H from CH2), 1.85 – 1.91 (1H, m, 1H from CH2), 1.97 -
2.06 (1H, m, 1H from CH2), 2.19 – 2.33 (3H, m, J 6.3, 1H from CH2 + CH2), 2.55 (1H, sxt, J
6.0, CH), 2.77 (1H, s, CHPh), 3.78 (1H, qd, J 6.6, 3.2, CHCH3), 6.20 (1H, dt, J 15.8, 6.9,
CH2CH=CH), 6.39 (1H, d, J 15.8, CH2CH=CH), 6.95 - 6.98 (1H, m, ArH), 7.18 - 7.22 (1H,
m, ArH), 7.23 - 7.39 (8H, m, ArH); δC (125 MHz, CDCl3) 16.2 (CH3), 22.9 (CH2), 26.4
(CH2), 32.0 (CH3), 33.0 (CH2), 34.9 (CH2), 38.5 (CH2), 42.2 (CHMe), 53.8 (CH), 63.2
(CHPh), 73.8 (quat. C), 125.9 (ArCH), 126.8 (ArCH), 127.0 (ArCH), 127.9 (ArCH), 128.5
(ArCH), 130.0 (CH2CH=CH or CH2CH=CH), 130.2 (CH2CH=CH or CH2CH=CH), 130.4
(ArCH), 137.7 (ArC), 137.7 (ArC), 217.2 (CO); m/z (ESI+) 394.5 ([M + NH4]+, 100%);
HRMS (ESI+) found 399.2301, expect 399.2295 for C26H32O2Na.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S14
rac-(4S,4aS,5R,6R,7S,9aR)-7-Methyl-5-(methyl-d)-6-phenyl-4-((S)-phenylmethyl-
d)decahydro-4aH-benzo[7]annulene-5,6-d2-4a,7-diol-d2 – 2b-D4
As described in general procedure E, reaction of rac-(3R,6S)-6-methyl-3-((E)-5-phenylpent-
4-en-1-yl)-6-(1-phenylpropa-1,2-dien-1-yl)tetrahydro-2H-pyran-2-one trans-1b (30.0 mg,
0.08 mmol, 1 equiv.), D2O (6.40 mL, 0.32 mol, 4000 equiv.) and SmI2 (6.40 mL, 0.64 mmol,
8 equiv.), after work-up and flash column chromatography (10% EtOAc:hexane → 20%
EtOAc:hexane) yielded 2b-D4 (7 mg, 23%) as a colourless oil; δH (400 MHz, CDCl3) 1.11
(3H, s CH3), 1.12 - 1.19 (2H, m, 1H from CH2 + 1H from CH2), 1.20 - 1.26 (1H, m, 1H from
CH2), 1.32 - 1.37 (1H, m, 1H from CH2), 1.41 - 1.47 (4H, m, CH2 + CDH2), 1.53 - 1.64 (2H,
m, 1H from CH2 + CH), 1.72 - 1.79 (1H, m, CH), 1.84 (1H, dd, J 15.3, 11.7, 1H from CH2),
1.98 - 2.08 (2H, m, 1H, CH2), 2.84 (1H, d, J 2.8, 1H from CDHPh), 7.07 (2H, d, J 7.3, ArH),
7.16 (1H, t, J 7.3, ArH), 7.21 - 7.27 (3H, m, ArH), 7.33 (2H, t, J 7.3, ArH), 7.39 - 7.44 (2H,
m, ArH); δC (125 MHz, CDCl3) 12.8 (t, J 19.1, CDH2), 25.8 (CH2), 26.4 (CH2), 26.6 (CH2),
28.2 (CH3), 30.8 (CH2), 34.4 (t, J 19.1, CDHPh), 42.4 (t, J 17.3, CDCH2D), 43.1 (CH2), 44.3
(CH), 45.2 (CH), 48.9 (t, J 19.1, CDPh), 74.7 (quat. C), 77.2 (quat. C), 125.7 (ArCH), 126.3
(ArCH), 128.2 (ArCH), 128.3 (ArCH), 129.1 (ArCH), 129.6 (ArCH), 141.2 (ArC), 145.3
(ArC); m/z (ESI+) 405.7 ([M + Na]+, 100%); HRMS (ESI+) found 405.2705, expect
405.2708 for C26H30D4O2Na.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S15
Ethyl (E)-2-(3-oxobutyl)-7-(4-(trifluoromethyl)phenyl)hept-6-enoate – S6
As described in general procedure F, ethyl 2-(3-oxobutyl)hept-6-enoate (0.22 g, 0.97 mmol, 1
equiv.), 4-(trifluoromethyl)styrene (0.43 mL, 2.92 mmol, 3 equiv.) and Grubbs’ catalyst
second generation (9.00 mg, 9.72 µmol, 1 mol%) in CH2Cl2 (2 mL) overnight at reflux with
subsequent work-up and purification by flash colum chromatography (toluene → 2%
EtOAc:toluene) yielded the named compound as a colourless oil (0.36 g, 99%); υmax / cm-1
2946, 1716, 1635, 1324, 1162, 1108; δH (500 MHz, CDCl3) 1.27 (3H, t, J 7.3, CH2CH3), 1.44
- 1.57 (3H, m, 1H from CH2 + CH2), 1.64 - 1.74 (1H, m, 1H from CH2), 1.83 (2H, q, J 7.5,
CH2), 2.14 (3H, s, CH3), 2.24 (2H, q, J 6.7, CH2), 2.33 - 2.42 (1H, m, 1H from CH2), 2.45
(1H, qd, J 7.9, 2.5, CH), 4.15 (2H, q, J 7.3, CH2CH3), 6.29 (1H, dt, J 15.8, 6.9, CH2CH=CH),
6.41 (1H, d, J 15.8, CH2CH=CH), 7.42 (2H, d, J 8.2, ArH), 7.54 (2H, d, J 7.9, ArH); δC (125
MHz, CDCl3) 14.3 (CH2CH3), 25.9 (CH2), 26.7 (CH2), 30.0 (CH3), 31.9 (CH2), 32.8 (CH2),
41.0 (CH2), 44.6 (CH), 60.3 (CH2CH3), 125.4 (q, J3 3.6, ArCH), 125.6 (q, J
1 271.6, CF3),
126.0 (ArCH), 129.0 (q, J2 32.7, ArCCF3), 129.1 (CH2CH=CH), 133.1 (CH2CH=CH), 141.1
(ArC), 175.6 (CO2Et), 208.0 (CO); m/z (ESI+) 393.4 ([M + Na]+, 100%); HRMS (ESI+)
found 393.1637, expect 393.1653 for C20H25O3F3Na.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S16
rac-(3R,6S)-6-Methyl-6-(1-phenyl-propa-1,2-dien-1-yl)-3-((E)-5-(4-
(trifluoromethyl)phenyl)pent-4-en-1-yl)tetrahydro-2H-pyran-2-one – trans-1c
As described in general procedure D, reaction of ethyl (E)-2-(3-oxobutyl)-7-(4-
(trifluoromethyl)phenyl)hept-6-enoate (0.25 g, 0.68 mmol, 1 equiv.), (3-bromoprop-1-yn-1-
yl)benzene (0.17 g, 0.88 mmol, 1.3 equiv.), SmI2 (27.0 mL, 2.72 mmol, 4 equiv.) and NiI2
(16.0 mg, 0.05 mmol, 2 mol% with respect to SmI2), after work-up and flash column
chromatography (5% EtOAc:hexane) yielded trans-1c as a yellow oil (combined yield for cis
and trans isomers: 24%, for trans-1c: 36 mg, 12%); υmax / cm-1
2934, 1728, 1614, 1324,
1162, 1119, 1067; δH (500 MHz, CDCl3) 1.53 - 1.59 (3H, m, 1H from CH2 + CH2), 1.62 (3H,
s, CH3), 1.64 - 1.72 (1H, m, 1H from CH2), 1.86 (1H, quin, J 6.4, 1H from CH2), 1.91 - 2.01
(1H, m, 1H from CH2), 2.12 (1H, sxt, J 6.9, 1H from CH2), 2.20 - 2.30 (3H, m, 1H from CH2
+ CH2), 2.40 - 2.48 (1H, m, CH), 5.11 (2H, s, C=CH2), 6.31 (1H, dt, J 15.7, 6.7,
CH2CH=CH), 6.42 (1H, d, J 15.9, CH2CH=CH), 7.24 - 7.30 (1H, m, ArH), 7.34 (2H, t, J 7.6,
ArH), 7.43 (4H, dd, J 13.1, 7.7, ArH), 7.54 (2H, d, J 8.1, ArH); δC (125 MHz, CDCl3) 22.7
(CH2), 26.4 (CH2), 28.1 (CH3), 31.0 (CH2), 31.8 (CH2), 32.9 (CH2), 38.6 (CH), 78.7
(C=CH2), 83.0 (quat. C), 110.2 (C=C=CH2), 124.2 (q, J1 271.6, CF3), 125.4 (q, J
3 3.6,
ArCH), 126.0 (ArCH), 127.5 (ArCH), 128.4 (ArCH), 128.6 (q, J2 32.7, ArCCF3), 128.9
(CH2CH=CH), 129.0 (ArCH), 133.1 (CH2CH=CH), 134.0 (ArC), 141.1 (ArC), 174.0 (CO),
207.4 (C=CH2); m/z (ESI+) 463.2 ([M + Na]+, 100%); HRMS (ESI+) found 463.1848, expect
463.1855 for C27H27O2F3Na.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S17
rac-(4S,4aS,5R,6R,7S,9aR)-5,7-Dimethyl-6-phenyl-4-(4-
(trifluoromethyl)benzyl)decahydro-4aH-benzo[7]annulene-4a,7-diol – 2c
As described in general procedure E, reaction of rac-(3R,6S)-6-methyl-6-(1-phenyl-propa-
1,2-dien-1-yl)-3-((E)-5-(4-(trifluoromethyl)phenyl)pent-4-en-1-yl)tetrahydro-2H-pyran-2-one
trans-1c (40.0 mg, 0.09 mmol, 1 equiv.), H2O (6.50 mL, 0.36 mol, 4000 equiv.) and SmI2
(7.30 mL, 0.73 mmol, 8 equiv.), after work-up and flash column chromatography (10%
EtOAc:hexane → 20% EtOAc:hexane) yielded 2c (10 mg, 24%) as a colourless oil; υmax /
cm-1
3458, 2953, 2872, 1623, 1451, 1321, 1186, 1121, 1085; δH (500 MHz, CDCl3) 1.12 (3H,
m, CHCH3), 1.14 - 1.19 (2H, m, 1H from CH2 + 1H from CH2), 1.22 - 1.27 (2H, m 1H from
CH2 + 1H from CH2), 1.40 - 1.51 (5H, m, CH2 + CH3), 1.53 - 1.65 (2H, m, 1H from CH2 +
CH), 1.78 (1H, tt, J 11.3, 4.1, CH), 1.85 (1H, dd, J 15.3, 11.8, 1H from CH2), 1.99 - 2.07 (2H,
m, CH2), 2.19 (1H, dd, J 13.2, 11.3, 1H from CH2Ph), 2.48 (1H, q, J 7.6, CHCH3), 2.91 (1H,
dd, J 13.2, 2.8, 1H from CH2Ph), 3.91 (1H, s, CHPh), 7.18 (2H, d, J 7.9, ArH-CF3), 7.23 -
7.27 (1H, ArH), 7.34 (2H, t, J 7.6, ArH), 7.41 (2H, d, J 7.3, ArH), 7.50 (2H, d, J 7.9, ArH-
CF3); δC (125 MHz, CDCl3) 13.2 (CH3), 25.7 (CH2), 26.4 (CH2), 26.6 (CH2), 28.3 (CH3), 30.8
(CH2), 34.7 (CH2), 42.9 (CHMe), 43.1 (CH2), 44.2 (CH), 45.1 (CH), 49.4 (CHPh), 74.7(quat.
C), 77.2 (quat. C), 125.1 (q, J3 3.6, ArCH), 125.4 (q, J
1 271.6, CF3) 126.4 (ArCH), 128.2 (q,
J2 31.8, ArCCF3), 128.4 (ArCH), 129.4 (ArCH), 129.6 (ArCH), 145.2 (ArC), 145.6 (ArC);
m/z (ESI+) 469.5 ([M + Na]+, 100%); HRMS (ESI+) found 469.2321, expect 469.2330 for
C27H33O2F3Na.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S18
Ethyl (E)-7-(4-bromophenyl)-2-(3-oxobutyl)hept-6-enoate – S7
As described in general procedure F, ethyl 2-(3-oxobutyl)hept-6-enoate (0.20 g, 0.88 mmol, 1
equiv.), Hoveyda-Grubbs II catalyst (5.50 mg, 8.80 µmol, 1 mol%) and 4-bromostyrene (0.49
g, 2.65 mmol, 3 equiv.) in CH2Cl2 (5 mL) after work-up and column chromatography on
silica gel eluting with (petroleum ether -10% EtOAc:petroleum ether) gave the title
compound as a yellow oil (0.15 g, 45%); νmax /cm-1
2935, 1716, 1487, 1445, 1401, 1366,
1154, 1096, 1072, 1026; δH (400 MHz, CDCl3) 1.27 (3H, t, J 7.1, CH2CH3), 1.41 - 1.56 (3H,
m, 1H from CH2 + CH2), 1.61 - 1.74 (1H, m, 1H from CH2), 1.78 - 1.86 (2H, m, CH2), 2.13
(3H, s, CH3), 2.17 - 2.24 (2H, m, CH2), 2.32 - 2.40 (1H, m, CH), 2.41 - 2.49 (2H, m,
CH2CO), 4.15 (2H, q, J 7.1, CH2CH3), 6.12 - 6.22 (1H, m, CH=CHPh), 6.27 - 6.36 (1H, m,
CH=CHPh), 7.20 (2H, d, J 8.6, ArH), 7.41 (2H, d, J 8.6, ArH); δC (100 MHz, CDCl3) 14.3
(CH3), 25.9 (CH2), 26.8 (CH2), 30.0 (CH3), 31.9 (CH2), 32.8 (CH2), 41.1 (CH2), 44.6 (CH),
60.3 (CH2CH3), 120.5 (ArC), 127.5 (ArCH), 129.1 (CH2CH=CH), 131.1 (CH2CH=CH),
131.5 (ArCH), 136.6 (ArC), 175.6 (CO2Et), 207.9 (CO); m/z (ESI+) 381.0 ([M+H]+, 100%).
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S19
rac-(3R,6S)-3-((E)-5-(4-Bromophenyl)pent-4-en-1-yl)-6-methyl-6-(1-phenyl-2l5-propa-1,2-
dien-1-yl)tetrahydro-2H-pyran-2-one – trans-1d
As described in general procedure D, reaction of ethyl (E)-7-(4-bromophenyl)-2-(3-
oxobutyl)hept-6-enoate (0.24 g, 0.63 mmol, 1 equiv.), (3-bromoprop-1-yn-1-yl)benzene (0.16
g, 0.82 mmol, 1.3 equiv.), SmI2 (23.0 mL, 2.22 mmol, 3.5 equiv.) and NiI2 (14.0 mg, 0.04
mmol, 2 mol% with respect to SmI2), after work-up and flash column chromatography (5%
EtOAc:hexane) yielded trans-1d as a yellow oil (combined yield for cis and trans isomers:
22%, for trans-1d: 30 mg, 11%); υmax / cm-1
2934, 1726, 1487, 1216, 1072; δH (500 MHz,
CDCl3) 1.51 - 1.59 (3H, m, 1H from CH2 + CH2), 1.62 (3H, m, CH3), 1.63 - 1.71 (1H, m, 1H
from CH2), 1.86 (1H, quin, J 6.6, 1H from CH2), 1.92 - 1.98 (1H, m, 1H from CH2), 2.11
(1H, sxt, J 7.3, 1H from CH2), 2.19 - 2.27 (3H, m, 1H from CH2 + CH2), 2.40 - 2.47 (1H, m,
CH), 5.12 (2H, s, C=CH2), 6.20 (1H, dt, J 15.8, 6.9, CH2CH=CH), 6.32 (1 H, d, J 15.8,
CH2CH=CH), 7.18 - 7.21 (2H, m, ArH), 7.26 - 7.30 (1H, m, ArH), 7.31 - 7.35 (2H, m, ArH),
7.39 - 7.42 (2H, m, ArH), 7.43 - 7.46 (2H, m, ArH); δC (125 MHz, CDCl3) 22.7 (CH2) 26.5
(CH2) 28.1 (CH3) 31.0 (CH2) 31.9 (CH2) 32.9 (CH2) 38.6 (CH) 78.7 (C=CH2) 83.0 (quat. C)
110.3 (C=C=CH2) 120.5 (ArC) 127.5 (ArCH) 128.4 (ArCH) 129.0 (ArCH) 129.1
(CH2CH=CH) 131.1 (CH2CH=CH) 131.5 (ArCH) 134.0 (ArC) 136.6 (ArC) 173.9 (CO)
207.4 (C=CH2); m/z (ESI+) 485.5 ([M + K]+, 100%); HRMS (ESI+) found 451.1267, expect
451.1267 for C26H28O2Br.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S20
rac-(4S,4aS,5R,6R,7S,9aR)-4-(4-Bromobenzyl)-5,7-dimethyl-6-phenyldecahydro-4aH-
benzo[7]annulene-4a,7-diol – 2d
As described in general procedure E, reaction of rac-(3R,6S)-3-((E)-5-(4-bromophenyl)pent-
4-en-1-yl)-6-methyl-6-(1-phenyl-propa-1,2-dien-1-yl)tetrahydro-2H-pyran-2-one trans-1d
(70 mg, 0.16 mmol, 1 equiv.), H2O (11.2 mL, 0.62 mol, 4000 equiv.) and SmI2 (12.5 mL,
1.24 mmol, 8 equiv.), after work-up and flash column chromatography (10% EtOAc:hexane
→ 20% EtOAc:hexane) yielded 2d (14 mg, 20%) as a white solid; m. p. 151 – 155 °C
(MeOH); υmax / cm-1
3472, 2962, 2924, 1622, 1492, 1470, 1432, 1016; δH (500 MHz, CDCl3)
1.12 (3H, s, CH3), 1.14 - 1.16 (1H, m, 1H from CH2), 1.21 - 1.26 (1H, m, 1H from CH2), 1.27
– 1.33 (1H, m, 1H from CH2), 1.43 (3H, d, J 7.6, CH3), 1.45 - 1.48 (2H, m, CH2), 1.52 - 1.59
(2H, m, 1H from CH2 + CH), 1.60 - 1.65 (1H, m, 1H from CH2), 1.72 (1H, tt, J 7.6, 3.7, CH),
1.84 (1H, dd, J 15.3, 11.8, 1H from CH2), 1.99 - 2.11 (3H, m, 1H from CH2Ph + CH2), 2.47
(1H, q, J 7.7, CHCH3), 2.80 (1H, dd, J 13.6, 3.5, 1H from CH2Ph), 3.90 (1H, s, CHPh), 6.94
(2H, d, J 8.2, ArH), 7.23 - 7.28 (2H, m, ArH), 7.31 - 7.38 (4H, m, ArH), 7.41 (2H, d, J 7.3,
ArH); δC (125 MHz, CDCl3) 13.2 (CH3), 25.7 (CH2), 26.4 (CH2), 26.5 (CH2), 28.3 (CH3),
30.8 (CH2), 34.2 (CH2), 42.9 (CHMe), 43.1 (CH2), 44.3 (CH), 45.1 (CH), 49.4 (CHPh), 74.7
(quat. C), 77.2 (quat. C), 119.4 (ArC), 126.4 (ArCH), 128.4 (ArCH), 129.6 (ArCH), 130.8
(ArCH), 131.2 (ArCH), 140.3 (ArC), 145.2 (ArC); m/z (ESI+) 479.3 ([M + Na]+, 100%);
HRMS (ESI+) found 479.1570, expect 479.1562 for C26H33O2BrNa.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S21
Ethyl (E)-2-(3-oxobutyl)-7-(p-tolyl)hept-6-enoate – S8
As described in general procedure F, ethyl 2-(3-oxobutyl)hept-6-enoate (0.60 g, 2.65 mmol, 1
equiv.), 4-methylstyrene (1.00 g, 7.96 mmol, 3 equiv.) and Grubbs’ catalyst second
generation (45.0 mg, 53.1 µmol, 1 mol%) in CH2Cl2 (10 mL) overnight at reflux with
subsequent work-up and purification by flash colum chromatography (toluene → 2%
EtOAc:toluene) yielded the named compound as a colourless oil (0.58 g, 69%); υmax / cm-1
2934, 1717, 1512, 1446, 1367, 1155; δH (500 MHz, CDCl3) 1.27 (3H, t, J 7.3, CH2CH3), 1.44
- 1.54 (3H, m, 1H from CH2 + CH2), 1.64 - 1.73 (1H, m, 1H from CH2), 1.82 (2H, q, J 7.3,
CH2), 2.13 (3H, s, CH3), 2.20 (2H, q, J 6.7, CH2), 2.33 (3H, s, CH3), 2.34 - 2.39 (1H, m, 1H
from CH2), 2.44 (2H, td, J 7.5, 3.9, CH), 4.15 (2H, q, J 7.3, CH2CH3), 6.13 (1H, dt, J 15.7,
7.0, CH2CH=CH), 6.34 (1H, d, J 15.8, CH2CH=CH), 7.10 (2H, d, J 7.9, ArH), 7.23 (2H, d, J
8.2, ArH); δC (125 MHz, CDCl3) 14.3 (CH2CH3), 21.1 (ArCH3), 25.9 (CH2), 27.0 (CH2), 29.9
(CH3), 31.8 (CH2), 32.7 (CH2), 41.1 (CH2), 44.6 (CH), 60.2 (CH2CH3), 125.8 (ArCH), 129.1
(CH2CH=CH + CH2CH=CH), 130.0 (ArCH), 134.8 (ArC), 136.5 (ArC), 175.7 (CO2Et),
208.0 (CO); m/z (ESI+) 317.5 ([M + H]+, 100%); HRMS (ESI+) found 339.1931, expect
339.1936 for C20H28O3Na.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S22
rac-(3R,6S)-6-Methyl-6-(1-phenyl-2l5-propa-1,2-dien-1-yl)-3-((E)-5-(p-tolyl)pent-4-en-1-
yl)tetrahydro-2H-pyran-2-one – trans-1e
As described in general procedure D, reaction of ethyl (E)-2-(3-oxobutyl)-7-(p-tolyl)hept-6-
enoate (0.23 g, 0.71 mmol, 1 equiv.), (3-bromoprop-1-yn-1-yl)benzene (0.18 g, 0.95 mmol,
1.3 equiv.), SmI2 (25.0 mL, 2.49 mmol, 3.5 equiv.) and NiI2 (16.0 mg, 0.05 mmol, 2 mol%
with respect to SmI2), after work-up and flash column chromatography (5% EtOAc:hexane)
yielded trans-1e as a yellow oil (combined yield for cis and trans isomers: 20%, for trans-1e:
28 mg, 10%); υmax / cm-1
2923, 1726, 1512, 1492, 1446, 1215, 1091; δH (400 MHz, CDCl3)
1.51 - 1.55 (2H, m, CH2), 1.59 - 1.71 (5H, m, CH2 + CH3), 1.85 (1H, quin, J 6.6, 1H from
CH2), 1.92 - 2.00 (1H, m, 1H from CH2), 2.11 (1H, sxt, J 6.8, 1H from CH2), 2.18-2.25 (3H,
m, 1H from CH2 + CH2), 2.33 (3H, s, ArCH3), 2.39 - 2.47 (1H, m, CH), 5.11 (2H, s, C=CH2),
6.17 (1H, dt, J 15.6, 7.1, CH2CH=CH), 6.35 (1H, d, J 15.9, CH2CH=CH), 7.10 (2H, d, J 7.8,
ArH), 7.23 (2H, d, J 8.3, ArH), 7.28 - 7.30 (1H, m, ArH), 7.31 - 7.36 (2H, m, ArH), 7.43 -
7.46 (2H, m, ArH); δC (125 MHz, CDCl3) 21.1 (ArCH3), 22.6 (CH2), 26.7 (CH2), 28.1 (CH3),
31.0 (CH2), 31.8 (CH2), 32.9 (CH2), 38.6 (CH), 78.7 (C=CH2), 82.9 (quat. C), 110.2
(C=C=CH2), 125.8 (ArCH), 127.5 (ArCH), 128.4 (ArCH), 128.9 (ArCH), 129.1 (ArCH),
129.2 (CH2CH=CH), 130.0 (CH2CH=CH), 134.0 (ArC), 134.9 (ArC), 136.6 (ArC), 174.0
(CO), 207.4 (C=CH2); m/z (ESI+) 387.2 ([M + H]+, 100%); HRMS (ESI+) found 387.2310,
expect 387.2319 for C27H31O2.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S23
rac-(4S,4aS,5R,6R,7S,9aR)-5,7-Dimethyl-4-(4-methylbenzyl)-6-phenyldecahydro-4aH-
benzo[7]annulene-4a,7-diol – 2e
As described in general procedure E, reaction of rac-(3R,6S)-6-methyl-6-(1-phenyl-2l5-
propa-1,2-dien-1-yl)-3-((E)-5-(p-tolyl)pent-4-en-1-yl)tetrahydro-2H-pyran-2-one trans-1e
(28.0 mg, 0.07 mmol, 1 equiv.), H2O (5.20 mL, 0.29 mol, 4000 equiv.) and SmI2 (5.80 mL,
0.58 mmol, 8 equiv.), after work-up and flash column chromatography (10% EtOAc:hexane
→ 20% EtOAc:hexane) yielded 2e (7 mg, 26%) as a yellow oil; υmax / cm-1
3486, 2965, 2879,
1514, 1479, 1398, 1085; δH (400 MHz, CDCl3) 1.11 (3H, s, CH3), 1.12 - 1.18 (1H, m, 1H
from CH2), 1.19 - 1.26 (1H, m, 1H from CH2), 1.29 - 1.34 (1H, m, 1H from CH2), 1.39 - 1.51
(5H, m, CH2 + CH3), 1.53 - 1.63 (3H, m, 1H from CH2 + 1H from CH2 + CH), 1.70 - 1.77
(1H, m, CH), 1.85 (1H, dd, J 15.4, 11.9, 1H from CH2), 1.98 - 2.09 (3H, m, 1H from CH2Ph
+ CH2), 2.31 (3H, s, ArCH3), 2.51 (1H, q, J 7.6, CHCH3), 2.82 (1H, dd, J 13.4, 3.3, 1H from
CH2Ph), 3.92 (1H, s, CHPh), 6.95 (2H, d, J 7.8, ArH), 7.06 (2H, d, J 7.8, ArH), 7.22 - 7.27
(1H, m, ArH), 7.33 (2H, dd, J 7.8, 7.1, ArH), 7.42 (2H, d, J 7.1, ArH); δC (125 MHz, CDCl3)
13.3 (CH3), 21.0 (ArCH3), 25.8 (CH2), 26.4 (CH2), 26.6 (CH2), 28.3 (CH3), 30.9 (CH2), 34.2
(CH2), 43.0 (CHMe), 43.2 (CH2), 44.4 (CH), 45.2 (CH), 49.4 (CHPh), 74.7 (quat. C), 77.2
(quat. C), 126.3 (ArCH), 128.3 (ArCH), 128.9 (ArCH), 129.0 (ArCH), 129.6 (ArCH), 135.1
(ArC), 138.0 (ArC), 145.3 (ArC); m/z (ESI+) 415.5 ([M + Na]+, 100%); HRMS (ESI+) found
415.2626, expect 415.2613 for C27H36O2Na.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S24
Ethyl (E)-7-(2-chlorophenyl)-2-(3-oxobutyl)hept-6-enoate – S9
As described in general procedure F, ethyl 2-(3-oxobutyl)hept-6-enoate (0.30 g, 1.33 mmol, 1
equiv.), 2-chlorostyrene (0.51 mL, 3.98 mmol, 3 equiv.) and Grubbs’ catalyst second
generation (12.0 mg, 13.3 µmol, 1 mol%) in CH2Cl2 (3 mL) overnight at reflux with
subsequent work-up and purification by flash colum chromatography (toluene → 2%
EtOAc:toluene) yielded the named compound as a colourless oil (0.29 g, 66%); υmax / cm-1
2935, 1718, 1470, 1440, 1367, 1156; δH (400 MHz, CDCl3) 1.27 (3H, t, J 7.1, CH2CH3), 1.43
- 1.58 (3H, m, 1H from CH2 + CH2), 1.64 - 1.75 (1H, m, 1H from CH2), 1.79 - 1.87 (2H, m,
CH2), 2.14 (3H, s, CH3), 2.26 (2H, q, J 6.6, CH2), 2.33 - 2.42 (1H, m, CH), 2.42 - 2.49 (2H,
m, CH2), 4.16 (2H, q, J 7.2, CH2CH3), 6.11 - 6.22 (1H, m, CH2CH=CH), 6.75 (1H, d, J 16.1,
CH2CH=CH), 7.09 - 7.23 (2H, m, ArH), 7.33 (1H, d, J 7.8, ArH), 7.49 (1H, d, J 7.7, ArH); δC
(100 MHz, CDCl3) 14.4 (CH3), 26.0 (CH2), 26.8 (CH2), 30.0 (CH3), 31.9 (CH2), 33.0 (CH2),
41.1 (CH2), 44.6 (CH), 60.3 (CH2CH3), 126.5 (2 × CH=CHPh), 126.6 (ArCH), 126.8
(ArCH), 128.0 (ArCH), 129.6 (ArCH), 133.2 (ArC), 135.8 (ArC), 175.7 (CO2Et), 208.0
(CO); m/z (ESI+) 337.3 ([M + H]+, 100%); HRMS (ESI+) found 359.1377, expect 359.1390
for C19H25O3ClNa.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S25
rac-(3R,6S)-3-((E)-5-(2-Chlorophenyl)pent-4-en-1-yl)-6-methyl-6-(1-phenyl-2l5-propa-1,2-
dien-1-yl)tetrahydro-2H-pyran-2-one – trans-1f
As described in general procedure D, reaction of ethyl ethyl (E)-7-(2-chlorophenyl)-2-(3-
oxobutyl)hept-6-enoate (0.36 g, 1.07 mmol, 1 equiv.), (3-bromoprop-1-yn-1-yl)benzene (0.27
g, 1.39 mmol, 1.3 equiv.), SmI2 (34.0 mL, 3.74 mmol, 3.5 equiv.) and NiI2 (16.0 mg, 74.6
µmol, 2 mol% with respect to SmI2), after work-up and flash column chromatography (5%
EtOAc:hexane) yielded trans-1f as a yellow oil (combined yield for cis and trans isomers:
20%, for trans-1f: 44 mg, 10%); υmax / cm-1
2929, 1945, 1721, 1492, 1469, 1215, 1074; δH
(400 MHz, CDCl3) 1.43 - 1.56 (6H, m, 1H from CH2 + CH2 + CH3), 1.55 - 1.64 (1H, m, 1H
from CH2), 1.74 - 1.82 (1H, m, 1H from CH2), 1.84 - 1.92 (1H, m, 1H from CH2), 2.03 (1 H,
sxt, J 6.7, 1H from CH2), 2.11 - 2.23 (3H, m, 1H from CH2 + CH2), 2.32 – 2.39 (1H, m, CH),
5.03 (2H, s, C=CH2), 6.07 - 6.17 (1H, m, CH2CH=CH), 6.67 (1H, d, J 15.7, CH2CH=CH),
7.05 (1H, t, J 7.3, ArH), 7.11 (1H, t, J 7.3 ArH), 7.15 - 7.21 (2H, m, ArH), 7.24 - 7.28 (2H,
m, ArH), 7.36 (2H, d, J 7.5, ArH), 7.41 (1H, d, J 7.6 ArH); δC (125 MHz, CDCl3) 22.9 (CH2),
26.8 (CH2), 28.4 (CH3), 31.5 (CH2), 32.3 (CH2), 33.2, (CH2), 38.6 (CH), 78.9 (C=CH2), 83.0
(quat. C), 110.5 (C=C=CH2), 126.4 (CH2CH=CH), 126.5 (CH2CH=CH), 126.8 (ArCH),
127.7 (ArCH), 128.1 (ArCH), 128.6 (ArCH), 129.2 (ArCH), 129.5 (ArCH), 132.7 (ArCH),
133.3 (ArC), 134.1 (ArC), 135.7 (ArC), 174.5 (CO), 208.3 (C=CH2); m/z (ESI+) 407.3 ([M +
H]+, 100%); HRMS (ESI+) found 429.1603, expect 429.1592 for C26H27O2ClNa.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S26
rac-(4S,4aS,5R,6R,7S,9aR)-4-(2-Chlorobenzyl)-5,7-dimethyl-6-phenyldecahydro-4aH-
benzo[7]annulene-4a,7-diol – 2f
As described in general procedure E, reaction of rac-(3R,6S)-6-methyl-6-(1-phenyl-2l5-
propa-1,2-dien-1-yl)-3-((E)-5-(p-tolyl)pent-4-en-1-yl)tetrahydro-2H-pyran-2-one trans-1f
(38.0 mg, 0.09 mmol, 1 equiv.), H2O (6.70 mL, 0.37 mol, 4000 equiv.) and SmI2 (7.5 mL,
0.75 mmol, 8 equiv.), after work-up and flash column chromatography (10% EtOAc:hexane
→ 20% EtOAc:hexane) yielded 2f (7 mg, 17%) as a white solid; m. p. 149 – 155 °C
(MeOH); υmax / cm-1
3329, 2918, 2852, 1448, 1386, 1264; δH (500 MHz, CDCl3) 1.11 (3H, s,
CH3), 1.12 - 1.20 (2H, m, 1H from CH2 + 1H from CH2), 1.22 - 1.24 (1H, m, 1H from CH2),
1.42 - 1.47 (2H, m, CH2), 1.48 (3H, d, J 7.6, CH3), 1.54 - 1.60 (2H, m, 1H from CH2 + CH),
1.86 (1H, dd, J 15.4, 11.7, 1H from CH2), 1.98 - 2.07 (4H, m, 1H from CH2 + CH + CH2),
2.37 (1 H, dd, J 13.1, 11.2, 1H from CH2Ph), 2.46 (1H, q, J 7.9, CHCH3), 2.94 (1H, dd, J
13.2, 4.4, 1H from CH2Ph), 3.91 (1H, s, CHPh), 7.05 - 7.08 (1H, m, ArH), 7.10 - 7.13 (2H,
m, ArH), 7.23 - 7.26 (1H, m, ArH), 7.29 - 7.31 (1H, m, ArH), 7.32 - 7.36 (2H, m, ArH), 7.40
- 7.44 (2H, m, ArH); δC (125 MHz, CDCl3)* 13.3 (CH3), 25.7 (CH2), 26.4 (CH2), 26.4 (CH2),
28.3 (CH3), 30.7 (CH2), 32.7 (CH2), 41.7 (CHMe), 43.0 (CH2), 43.1 (CH), 45.1 (CH), 49.5
(CHPh), 126.3 (ArCH), 126.4 (ArCH), 127.2 (ArCH), 128.3 (ArCH), 129.4 (ArCH), 129.6
(ArCH), 131.9 (ArCH), 134.2 (ArC), 138.7 (ArC), 145.3 (ArC); m/z (ESI+) 435.7 ([M +
Na]+, 100%). *two quaternary carbons not observed.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S27
Ethyl (E)-4,4-dimethylhepta-2,6-dienoate – S10
An oven-dried round bottom flask was flushed with N2 and loaded with
(carbethoxymethylene)triphenylphosphorane (12.0 g, 34.0 mmol, 1.7 equiv.) and dry toluene
(60 mL). To the stirred solution was added 2,2-dimethyl-4-pentenal (1.36 mL, 10.0 mmol, 1
equiv.) and the resulting solution was heated at 80 °C overnight. After cooling to room
temperature, the solvent was removed in vacuo and flash column chromatography (5%
Et2O:hexane) yielded S10 (3.31 g, 91%) as a colourless oil; υmax / cm-1
3091, 2982, 1707,
1679, 1382, 1302, 1279, 1186, 1018; δH (400 MHz, CDCl3) 1.01 (6H, s, 2 × CH3), 1.24 (3H,
t, J 7.2, CH2CH3), 2.06 (2H, dt, J 7.4, 1.1, CH2), 4.14 (2H, q, J 7.1, CH2CH3), 4.93 - 5.03
(2H, m, CH=CH2), 5.59 - 5.72 (2H, m, CH=CH2 + CH=CHCO2Et), 6.89 (1H, d, J 15.9,
CH=CHCO2Et); δC (100 MHz, CDCl3) 14.1 (CH3), 26.0 (2 × CH3), 36.6 (quat. C), 46.3
(CH2), 60.0 (CH2CH3), 117.6 (CH=CH2), 117.8 (CH=CHCO2Et), 134.1 (CH=CH2), 157.4
(CH=CHCO2Et), 166.9 (CO2Et); m/z (ESI+) 183.1 ([M + H]+, 100%); HRMS (ESI+) found
205.1205, expect 205.1204 for C11H18O2Na.
Methyl 4,4-dimethylhept-6-enoate – S11
Magnesium powder (2.70 g, 0.11 mol, 8 equiv.) was added slowly to a stirred solution of
ethyl (E)-4,4-dimethylhepta-2,6-dienoate (2.50 g, 13.7 mmol, 1 equiv.) in dry MeOH (130
mL) in an oven-dried round bottom flask flushed with N2.The reaction was stirred at room
temperature overnight and more magnesium powder (0.67 g, 27.5 mmol, 2 equiv.) was
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S28
added. After stirring for an additional 2 hours, the reaction was neutralised with 2 M HCl and
EtOAc was added (150 mL). The layers were separated and the aqueous layer was washed
with EtOAc (150 mL). The organic layers were combined, washed with brine (150 mL) and
dried over MgSO4. Concentration in vacuo and filtration through silica gel yielded S11 (1.21
g, 53%) as a crude colourless oil, which was taken through to the next step; δH (400 MHz,
CDCl3) 0.87 (6H, s, 2 × CH3), 1.53 - 1.59 (2H, m, CH2CH2CO2CH3), 1.95 (2H, dt, J 7.4, 1.1,
CH2CH=CH2), 2.25 - 2.31 (2H, m, CH2CO2CH3), 3.66 (3H, s, CO2CH3), 4.97 - 5.07 (2H, m,
CH=CH2), 5.80 (1H, m, CH=CH2); δC (100 MHz, CDCl3) 26.5 (2 × CH3), 29.3 (CH2), 32.7
(quat. C), 36.4 (CH2), 46.2 (CH2), 51.5 (CO2CH3), 117.1 (CH=CH2), 135.0 (CH=CH2), 174.7
(CO2Me).
Methyl (E)-4,4-dimethyl-7-phenylhept-6-enoate – S12
As described in general procedure F, methyl 4,4-dimethylhept-6-enoate (1.20 g, 7.05 mmol, 1
equiv.), styrene (2.40 mL, 21.2 mmol, 3 equiv.) and Grubb’s catalyst second generation (60.0
mg, 70.5 µmol, 1 mol%) in CH2Cl2 (18 mL) overnight at reflux with subsequent work-up and
purification by flash colum chromatography (toluene → 2% EtOAc:toluene) yielded the
named compound as a colourless oil (0.8 g, 46%); υmax / cm-1
3042, 2979, 1744, 1465, 1214,
1180; δH (400 MHz, CDCl3) 0.93 (6H, s, 2 × CH3), 1.60 - 1.67 (2H, m, CH2CH2CO2CH3),
2.12 (2H, dd, J 7.5, 0.8, CH2CH), 2.30 - 2.36 (2H, m, CH2CO2CH3), 3.68 (3H, s, CO2CH3),
6.18 - 6.29 (1H, m, CH=CHPh), 6.39 (1H, d, J 15.5, CH=CHPh), 7.22 (1H, t, J 7.2, ArH),
7.31 (2H, t, J 7.5, ArH), 7.37 (2H, d, J 7.3, ArH); δC (100 MHz, CDCl3) 26.6 (2 × CH3), 29.4
(CH2), 33.5 (quat. C), 36.5 (CH2), 45.4 (CH2), 51.6 (CO2CH3), 126.0 (ArCH), 126.9 (ArCH),
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S29
127.0 (CH=CHPh), 128.5 (ArCH), 132.4 (CH=CHPh), 137.7 (ArC), 174.7 (CO2Me); m/z
(ESI+) 269.3 ([M + Na]+, 100%).
2-(2-Iodoethyl)-2-methyl-1,3-dioxolane – S133
To a rapidly stirred solution of methyl vinyl ketone (3.00 mL, 36.0 mmol, 1 equiv.) and NaI
(6.50 g, 43.3 mmol, 1.2 equiv.) in MeCN (36 mL) was quickly added TMSCl (5.50 mL, 43.3
mmol, 1.2 equiv.) and the mixture was stirred for 25 minutes. Ethylene glycol (2.40 mL, 43.3
mmol, 1.2 equiv.) was added quickly and the reaction was stirred vigorously for another 25
minutes. The reaction mixture was then poured into a separating funnel containing 5%
NaHCO3 (15 mL) and hexane (60 mL), creating an aqueous bottom layer, the reaction
mixture in the middle and a top hexane layer. The bottom layer was removed and the organic
layers washed with 5% sodium thiosulfate (15 mL). The aqueous layers were combined and
extracted with EtOAc (2 × 60 mL). The organic layers were combined and dried over
MgSO4. The solvent was removed in vacuo, keeping the water bath below 25 °C, and flash
column chromatography (5% EtOAc:hexane) yielded the named compound as an orange oil
(1.2 g, 15%); δH (400 MHz, CDCl3) 1.29 - 1.33 (3H, m, CH3), 2.26 - 2.34 (2H, m, CH2), 3.13
- 3.20 (2H, m, CH2), 3.87 - 4.02 (4H, m, -OCH2CH2O-).
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S30
Methyl (E)-4,4-dimethyl-2-(2-(2-methyl-1,3-dioxolan-2-yl)ethyl)-7-phenylhept-6-enoate –
S14
As described in general procedure A, alkylation of methyl (E)-4,4-dimethyl-7-phenylhept-6-
enoate (0.22 g, 0.89 mmol, 1 equiv.) using LDA (0.75 M, 1.3 mL, 0.98 mmol, 1.1 equiv.),
then 2-(2-iodoethyl)-2-methyl-1,3-dioxolane (0.28 g, 1.22 mmol, 1.36 equiv.) and HMPA
(0.2 mL), after work-up and purification yielded S14 as an orange oil (75 mg, 17%); υmax /
cm-1
2983, 2893, 1714, 1479, 1392, 1210, 1181, 1080; δH (500 MHz, CDCl3) 0.89 (3H, s, J
4.4, CH3), 0.90 (3H, s, J 4.4, CH3), 1.29 (3H, s, CH3), 1.33 (1H, dd, J 14.2, 2.2, 1H from
CH2), 1.51 - 1.58 (2H, m, 1H from CH2 + 1H from CH2), 1.64 - 1.71 (2H, m, 1 H from CH2 +
1 H from CH2), 1.87 (1H, dd, J 14.2, 9.8, 1H from CH2), 2.10 (2H, dd, J 7.6, 0.9, CH2), 2.42 -
2.50 (1H, m, CH), 3.67 (3H, s, CO2CH3), 3.86 - 3.96 (4H, m, -OCH2CH2O-), 6.18 - 6.26 (1H,
m, CH=CHPh), 6.37 (1H, d, J 15.8, CH=CHPh), 7.21 (1H, tt, J 7.3, 1.3, ArCH), 7.31 (2H, t, J
7.3, ArCH), 7.36 (2H, d, J 7.3, ArCH); δC (125 MHz, CDCl3) 23.8 (CH3), 26.7 (CH3), 26.9
(CH3), 29.3 (CH2), 34.2 (quat. C), 36.7 (CH2), 41.4 (CH), 44.4 (CH2), 45.9 (CH2), 51.5
(CO2CH3), 64.6 (2 × -OCH2CH2O-), 109.6 (C-OCH2CH2O-), 126.0 (ArCH), 126.9 (ArCH),
127.2 (CH=CHPh), 128.5 (ArCH), 132.4 (CH=CHPh), 137.7 (ArC), 177.6 (CO2Me); m/z
(ESI+) 383.5 ([M + Na]+, 100%); HRMS (ESI+) found 383.2211, expect 383.2198 for
C22H32O4Na.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S31
Methyl (E)-4,4-dimethyl-2-(3-oxobutyl)-7-phenylhept-6-enoate – S15
As described in general procedure B, reaction of methyl (E)-4,4-dimethyl-2-(2-(2-methyl-1,3-
dioxolan-2-yl)ethyl)-7-phenylhept-6-enoate (0.21 g, 0.58 mmol, 1 equiv.) and p-
toluenesulfonic acid monohydrate (0.22 g, 1.17 mmol, 2 equiv.) in acetone (10 mL), after
work-up and purification yielded S15 as a pale yellow oil (0.15 g, 83%); υmax / cm-1
2958,
1729, 1714, 1465, 1365, 1186, 1156; δH (500 MHz, CDCl3) 0.89 (3H, s, J 4.4, CH3), 0.90
(3H, s, J 4.4, CH3), 1.31 (1H, dd, J 14.2, 2.5, 1H from CH2), 1.78 (2H, q, J 7.6, CH2), 1.86
(1H, dd, J 14.2, 9.8, 1H from CH2), 2.08 - 2.12 (5H, m, CH2 + CH3), 2.41 (2H, q, J 7.4, CH2),
2.46 - 2.53 (1H, m, CH), 3.67 (3H, s, CO2CH3), 6.17 - 6.25 (1H, m, CH=CHPh), 6.38 (1H, d,
J 15.8, CH=CHPh), 7.20 (1H, tt, J 7.3, 1.3, ArCH), 7.30 (2H, t, J 7.3, ArCH), 7.36 (2H, d, J
7.6, ArCH); δC (125 MHz, CDCl3) 26.6 (CH3), 26.9 (CH3), 28.5 (CH2), 29.9 (CH3), 34.1
(quat. C), 40.5 (CH), 40.8 (CH2), 44.2 (CH2), 45.7 (CH2), 51.5 (CO2CH3), 125.9 (ArCH),
126.9 (ArCH), 127.0 (CH=CHPh), 128.4 (ArCH), 132.4 (CH=CHPh), 137.6 (ArC), 177.1
(CO2Me), 207.6 (CO); m/z (ESI+) 339.4 ([M + Na]+, 100%); HRMS (ESI+) found 339.1934,
expect 339.1936 for C20H28O3Na.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S32
rac-(3S,6S)-3-((E)-2,2-Dimethyl-5-phenylpent-4-en-1-yl)-6-methyl-6-(1-phenyl-2l5-propa-
1,2-dien-1-yl)tetrahydro-2H-pyran-2-one – trans-1g
As described in general procedure D, reaction of methyl (E)-4,4-dimethyl-2-(3-oxobutyl)-7-
phenylhept-6-enoate (0.10 g, 0.32 mmol, 1 equiv.), (3-bromoprop-1-yn-1-yl)benzene (0.08 g,
0.41 mmol, 1.3 equiv.), SmI2 (11 mL, 1.11 mmol, 3.5 equiv.) and NiI2 (7 mg, 22.1 µmol, 2
mol % with respect to SmI2), after work-up and flash column chromatography (5%
EtOAc:hexane) yielded trans-1g as a yellow oil (combined yield for cis and trans isomers:
26%, for trans-1g: 13 mg, 13%); δH (500 MHz, CDCl3) 0.87 (3H, s, J 4.4, CH3), 0.88 (3H, s,
J 4.4, CH3), 1.17 (1H, dd, J 14.2, 5.4, 1H from CH2), 1.62 - 1.70 (4H, m, 1H from CH2 +
CH3), 1.83 - 1.91 (1H, m, 1H from CH2), 2.01 - 2.13 (2H, m, CH2), 2.15 - 2.22 (1H, m, 1H
from CH2), 2.25 (1H, dd, J 14.2, 4.1, 1H from CH2), 2.27 - 2.34 (1H, m, 1H from CH2), 2.51
- 2.58 (1H, m, CH), 5.14 (2H, s, C=CH2), 6.19 - 6.26 (1H, m, CH=CHPh), 6.32 (1H, d, J
15.8, CH=CHPh), 7.21 (1H, tt, J 7.3, 1.6, ArCH), 7.27 - 7.32 (3H, m, ArCH), 7.32 - 7.37
(4H, m, ArCH), 7.47 (2H, d, J 7.3, ArCH); δC (125 MHz, CDCl3) 26.1 (CH2), 26.9 (CH3),
26.9 (CH3), 28.8 (CH3), 32.4 (CH2), 34.3 (quat. C), 35.2 (CH), 42.9 (CH2), 45.9 (CH2), 78.7
(C=CH2), 82.7 (quat. C), 110.4 (C=C=CH2), 126.0 (ArCH), 126.9 (ArCH), 127.2 (ArCH),
127.5 (ArCH), 128.5 (ArCH), 128.9 (ArCH), 132.4 (CH2CH=CH and CH2CH=CH), 133.7
(ArC), 137.7 (ArC), 175.0 (CO), 207.3 (C=CH2); m/z (ESI+) 423.5 ([M + Na]+, 100%).
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S33
General Procedure G: Sonogashira reaction
5-Phenylpent-4-yn-1-ol – S164
An oven dried flask was degassed with N2 and loaded with THF (25 mL), DIPA (10 mL),
iodobenzene (2.70 mL, 24.1 mmol, 2 eq.) and 4-pentyn-1-ol (1.10 mL, 13.4 mmol, 1 equiv.).
PdCl2(PPh3)2 (173 mg, 0.25 mmol, 2 mol%) and CuI (30 mg, 0.16 mmol, 1 mol%) were
added to the mixture, which was heated under reflux for 18 hours. The reaction mixture was
filtered through celite, the residue washed and the filtrate concentrated in vacuo. The crude
product was purified by flash column chromatography (15% → 25% EtOAc:petroleum ether)
to give the named compound as a dark orange oil (1.55 g, 78%); δH (400 MHz, CDCl3) 1.82
(2H, quin, J 6.6, CH2), 2.50 (2H, t, J 7.1, CH2), 2.74 (1H, br. s, OH), 3.76 (2H, t, J 5.2, CH2),
7.19 - 7.30 (3H, m, ArH), 7.36 - 7.41 (2H, m, ArH); δC (100 MHz, CDCl3) 15.8 (CH2), 31.2
(CH2), 61.3 (CH2), 80.9 (C≡C), 89.3 (C≡C), 123.6 (ArC), 127.5 (ArCH), 128.1, (ArCH),
131.4, (ArCH).
(5-Iodopent-1-yn-1-yl)benzene – S174
As described in general procedure C, reaction of 5-phenylpent-4-yn-1-ol (0.15 g, 0.94 mmol,
1 equiv.), PPh3 (0.37 g, 1.43 mmol, 1.5 equiv.), imidazole (95.0 mg, 1.46 mmol, 1.5 equiv.)
and I2 (0.36 g, 1.42 mmol, 1.5 equiv.) after work-up and flash column chromatography
(hexane) yielded the named compound as a colourless oil (0.18 g, 72%); δH (400 MHz,
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S34
CDCl3) 2.11 (2H, quin, J 6.8, CH2), 2.57 (2H, t, J 6.7, CH2), 3.38 (2H, t, J 6.8, CH2), 7.27 -
7.33 (3H, m, ArH), 7.36 - 7.45 (2H, m, ArH); δC (100 MHz, CDCl3) 5.4 (CH2), 20.4 (CH2),
32.1 (CH2), 81.7 (C≡C), 87.8 (C≡C), 123.5 (ArC), 127.8 (ArCH), 128.2 (ArCH), 131.6
(ArCH).
Ethyl 2-(3-oxobutyl)-7-phenylhept-6-ynoate – S18
As described in general procedure A, treatment of ethyl 4-(2-methyl-1,3-dioxolan-2-
yl)butanoate (1.00 g, 4.94 mmol, 1 equiv.) in THF (2 mL) with 2.0 M LDA in hexane (3.50
mL, 5.50 mmol, 1.1 equiv.), followed by addition of (5-bromopent-1-yn-1-yl)benzene (1.32
g, 5.93 mmol, 1.2 equiv.) in HMPA (1.0 mL), after work-up gave the crude acetal protected
keto-ester, which was used without further purification. As described in general procedure B,
reaction of the crude ester with p-toluenesulfonic acid monohydrate (1.89 g, 9.89 mmol, 2
equiv.) in acetone (50 mL), after work-up and purification by column chromatography on
silica gel (petroleum ether → CH2Cl2:petroleum ether) gave the title compound (0.98 g, 66%
over 2 steps) as a colourless oil; νmax /cm-1
2937, 1716, 1598, 1490, 1366, 1257, 1153, 1096,
1069, 1025; δH (500 MHz, CDCl3) 1.27 (3H, t, J 7.1, CH2CH3), 1.57 - 1.70 (3H, m, 1H from
CH2 + CH2), 1.76 - 1.82 (1H, m, 1H from CH2), 1.85 (2H, q, J 7.8, CH2), 2.13 (3H, s, CH3),
2.37 - 2.49 (5H, m, CH + 1H from CH2 + 1H from CH2 + CH2), 4.16 (2H, q, J 7.1, CH2CH3),
7.26 - 7.31 (3H, m, ArH), 7.37 - 7.41 (2H, m, ArH); δC (125 MHz, CDCl3) 14.3 (CH3), 19.2
(CH2), 25.8 (CH2), 26.3 (CH2), 30.0 (CH3), 31.4 (CH2), 41.0 (CH2), 44.3 (CH), 60.3
(CH2CH3), 81.0 (PhC≡C), 89.4 (PhC≡C), 123.8 (ArC), 127.6 (ArCH), 128.2 (ArCH), 131.5
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S35
(ArCH), 175.5 (CO2Et), 207.9 (CO); m/z (ESI+) 301.3 ([M+H]+, 100%); HRMS (ESI+)
found 323.1613, expect 323.1623 for C19H24O3Na.
(3-Bromoprop-1-ynyl)dimethyl(phenyl)silane – S192
A solution of LDA was prepared by adding n-BuLi (1.54 M solution in hexane, 11.4 mL,
17.6 mmol, 1.1 equiv.) to diisopropylamine (2.40 g, 17.6 mmol, 1.1 equiv.) in Et2O (27 mL)
at -78 °C under N2 and stirring for 1 h. To this solution was added propargylic bromide (80%
solution in toluene, 1.78 mL, 16.0 mmol, 1 equiv.) and the reaction was stirred for 1 h before
the addition of chlorodimethyl(phenyl)silane (2.68 g, 16.0 mmol, 1 equiv.) and the resulting
reaction mixture allowed to warm to room temperature overnight. The reaction was quenched
by the addition of aqueous saturated NH4Cl (15 mL) and the aqueous layer extracted with
Et2O (3 × 30 mL). The combined organic layers were washed with brine (20 mL), dried
(Na2SO4) and concentrated in vacuo to yield the crude product. Purification by column
chromatography on silica gel eluting with 1:80 Et2O in pentane, gave the title compound
(3.70 g, 91%) as a yellow oil; δH (500 MHz, CDCl3) 0.31 (6H, s, Si(CH3)2Ph), 3.82 (2H, s,
CH2), 7.22-7.27 (3H, m, ArH), 7.48-7.50 (2H, m, ArH); δC (100 MHz, CDCl3) -1.3
(Si(CH3)2Ph), -1.1 (Si(CH3)2Ph), 14.5 (CH2), 90.3 (C≡CCH2), 101.6 (C≡CSi), 127.9 (ArCH),
133.6 (ArCH), 133.8 (ArCH), 136.2 (ArC).
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S36
(3R,6S)-6-(1-(Dimethyl(phenyl)silyl)-propa-1,2-dien-1-yl)-6-methyl-3-(5-phenylpent-4-yn-
1-yl)tetrahydro-2H-pyran-2-one – trans-1h
As described in general procedure D, reaction of methyl (E)-4,4-dimethyl-2-(3-oxobutyl)-7-
phenylhept-6-enoate (109 mg, 0.44 mmol, 1 equiv.), (3-bromoprop-1-
ynyl)dimethyl(phenyl)silane (112 mg, 0.57 mmol, 1.3 equiv.), SmI2 (13.0 mL, 1.33 mmol, 3
equiv.) and NiI2 (10.0 mg, 0.03 mmol, 2 mol % with respect to SmI2), after work-up and flash
column chromatography (petroleum ether → 5% EtOAc:petroleum ether) yielded trans-1h as
a colourless oil (combined yield for cis and trans isomers: 41%, for trans-1h: 73 mg, 21%);
νmax /cm-1
2954, 1927, 1731, 1489, 1428, 1249, 1098; δH (500 MHz, CDCl3) 0.35 - 0.38 (3H,
s, SiCH3), 0.45 - 0.49 (3H, s, SiCH3), 1.33 (3H, s, CH3), 1.35 - 1.49 (4H, m, 1H from CH2 +
1H from CH2 + CH2), 1.58 - 1.64 (1H, m, 1H from CH2), 1.70 - 1.83 (4H, m, CH2 + CH2),
1.89 (1H, ddd, J 13.7, 7.9, 5.5, 1H from CH2), 2.27 (2H, td, J 7.0, 2.4, CH), 4.53 (2H, s,
C=CH2), 7.18 - 7.33 (8H, m, ArH), 7.47 - 7.51 (2H, m, ArH); δC (125 MHz, CDCl3) -1.9
(SiCH3), -1.5 (SiCH3), 19.4 (CH), 22.8 (CH2), 26.1 (CH2), 29.6 (CH3), 30.7 (CH2), 33.3
(CH2), 38.3 (CH2), 72.3 (C=C=CH2), 80.9 (C≡CPh), 84.8 (quat. C), 89.7 (C≡CPh), 102.7
(C=C=CH2), 127.5 (ArCH), 127.8 (ArCH), 128.2 (ArCH), 129.2 (ArCH), 131.5 (ArCH),
131.9 (ArC), 134.1 (ArCH), 137.8 (ArC), 173.6 (CO), 207.9 (C=C=CH2); m/z (ESI+) 429.0
([M+H]+, 100%); HRMS (ESI+) found 451.2048, expect 451.2069 for C28H32O2SiNa.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S37
6-Allyl-6-methyltetrahydro-2H-pyran-2-one - S205
As described in general procedure D, reaction of methyl 5-oxohexanoate (300 mg, 1.90
mmol, 1 equiv.), allyl bromide (252 mg, 2.09 mmol, 1.1 equiv.), SmI2 (76.0 mL, 7.59 mmol,
3 equiv.) and NiI2 (48.0 mg, 0.15 mmol, 2 mol % with respect to SmI2), after work-up and
flash column chromatography (petroleum ether → 10% EtOAc:petroleum ether) yielded S20
as a colourless oil (245 mg, 84%); δH (400 MHz, CDCl3) 1.37 (3H, s, CH3), 1.63 - 1.71 (1H,
m, 1H from CH2), 1.77 - 1.93 (3H, m, 1H from CH2 + CH2), 2.40 - 2.58 (4H, m, CH2 + CH2),
5.10 - 5.19 (2H, m, CH=CH2), 5.80 (1H, ddt, J 14.5, 10.2, 7.3, CH=CH2); δC (100 MHz,
CDCl3) 16.5 (CH2), 26.3 (CH3), 29.3 (CH2), 31.4 (CH2), 46.1 (CH2CH=CH2), 83.6 (quat. C),
119.4 (CH=CH2), 132.3 (CH=CH2), 171.2 (CO).
6-Cinnamyl-6-methyltetrahydro-2H-pyran-2-one – S215
As described in general procedure F, methyl 4,4-dimethylhept-6-enoate 6-allyl-6-
methyltetrahydro-2H-pyran-2-one (500 mg, 3.57 mmol, 1 equiv.), trans-stilbene (1.93 g, 10.7
mmol, 3 equiv.) and Hoveyda–Grubbs second generation catalyst (52.0 mg, 82.0 µmol, 2.3
mol%) in CH2Cl2 (10 mL) overnight at reflux with subsequent work-up and purification by
flash column chromatography (petroleum ether → 2% EtOAc:petroleum ether) yielded the
named compound as a yellow oil (300 mg, 40%); δH (400 MHz, CDCl3) 1.34 (3H, s, CH3),
1.59 - 1.67 (2H, m, CH2), 1.73 - 1.87 (2H, m, CH2), 2.33 - 2.47 (2H, m, CH2), 2.50 (2H, dd, J
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S38
7.4, 1.1, CH2CH=CHAr), 6.12 (1H, dt, J 15.7, 7.5, PhCH=CH), 6.39 (1H, d, J 15.7,
PhCH=CH), 7.12 - 7.31 (5H, m, ArH); δC (100 MHz, CDCl3) 16.5 (CH2), 26.4 (CH3), 29.3
(CH2), 31.6 (CH2), 45.4 (CH2), 84.0 (quat. C), 123.8 (PhCH=CH), 126.1 (ArCH), 127.4
(ArCH), 128.5 (ArCH), 134.2 (PhCH=CH), 136.9 (ArC), 171.2 (CO).
(E)-5-Phenylpent-4-en-1-ol – S226
To a solution of LiAlH4 (1.04 g, 27.3 mmol, 3 equiv.) in THF (16 mL) was added 5-
phenylpent-4-yn-1-ol (1.46 g, 9.11 mmol, 1 equiv.) dropwise at 0 °C. The reaction mixture
was stirred at 60 °C over night. Once complete and cooled to 0 °C, the reaction was diluted
with ether and carefully quenched with H2O. After the addition of Rochelle’s salt, the layers
were separated and the aqueous layer extracted with EtOAc (3 × 20 mL). The combined
organic layers were washed with brine (30 mL), dried over Na2SO4 and concentrated in
vacuo. The compound was purified using flash column chromatography (petroleum ether →
5% → 10% → 20% EtOAc:petroleum ether), yielding the named compound as an orange oil
(1.33 g, 89%); δH (400 MHz, CDCl3) 1.73 – 1.82 (2H, m, CH2), 2.07 (1H, s, OH), 2.29 – 2.37
(2H, m, CH2), 3.71 (2H, t, J 6.4, CH2OH), 6.26 (1H, dt, J 15.7, 6.9, CH2CH=CH), 6.45 (1H,
d, J 15.9, CH2CH=CH), 7.21 – 7.26 (1H, m, ArH), 7.28 – 7.42 (4H, m, ArH); δC (100 MHz,
CDCl3) 29.3 (CH2), 32.1 (CH2), 62.2 (CH2), 125.8 (ArCH), 126.9 (ArCH), 128.4 (ArCH),
130.0 (CH=CHPh), 130.2 (CH=CHPh), 137.5 (ArC).
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S39
(E)-(5-Iodopent-1-en-1-yl)benzene - S237
As described in general procedure C, reaction of (E)-5-phenylpent-4-en-1-ol (1.16 g, 7.16
mmol, 1 equiv.), PPh3 (2.82 g, 16.8 mmol, 1.5 equiv.), imidazole (0.73 g, 16.8 mmol, 1.5
equiv.) and I2 (2.73 g, 16.8 mmol, 1.5 equiv.), after work-up and flash column
chromatography (hexane) yielded the title compound as a colourless oil (1.65 g, 85%); δH
(400 MHz, CDCl3) 1.93 (2H, quin, J 7.0, CH2), 2.27 (2H, qd, J 7.1, 1.4, CH2I), 3.16 (2H, t, J
6.9, CH2CH=CH), 6.08 (1H, dt, J 15.8, 7.0, CH2CH=CH), 6.39 (1H, d, J 15.8, CH2CH=CH),
7.14 (1H, tt, J 6.5, 1.5, ArH), 7.20 - 7.30 (4H, m, ArH); δC (100 MHz, CDCl3) 6.3 (CH2), 32.8
(CH2), 33.5 (CH2), 126.0 (ArCH), 127.1 (ArCH), 128.3 (ArCH), 128.5 (CH=CHPh), 131.3
(CH=CHPh), 137.4 (ArC).
(3R,6S)-6-Cinnamyl-6-methyl-3-((E)-5-phenylpent-4-en-1-yl)tetrahydro-2H-pyran-2-one –
trans-1i
As described in general procedure A, alkylation of (S)-6-cinnamyl-6-methyltetrahydro-2H-
pyran-2-one (250 mg, 1.08 mmol, 1 equiv.) using LDA (1 M, 1.22 mL, 1.20 mmol, 1.1
equiv.), then (E)-(5-iodopent-1-en-1-yl)benzene (887 mg, 3.25 mmol, 2.7 equiv.) in HMPA
(0.5 mL), after work-up and purification yielded trans-1i as a colourless oil (197 mg, 49%);
νmax /cm-1
2975, 2944, 1721, 1494, 449, 1380, 1360, 1298, 1199, 1110; δH (400 MHz, CDCl3)
1.41 - 1.45 (3H, s, CH3), 1.54 - 1.79 (5H, m, 1H from CH2 + CH2 + CH2), 1.85 - 2.04 (3H, m,
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S40
1H from CH2 + CH2), 2.24 (2H, q, J 7.1, CH2), 2.40 - 2.48 (1H, m, CH), 2.50 - 2.62 (2H, m,
CCH2CH=CH), 6.13 - 6.25 (2H, m, 2 × PhCH=CH), 6.36 - 6.50 (2H, m, 2 × PhCH=CH),
7.17 - 7.26 (2H, m, ArH), 7.27 - 7.39 (8H, m, ArH); δC (100 MHz, CDCl3) 22.3 (CH2), 26.7
(CH2), 27.5 (CH3), 31.0 (CH2), 31.4 (CH2), 32.9 (CH2), 39.5 (CH), 44.6 (CCH2CH=CH),
83.8 (quat. C), 123.9 (PhCH=CH), 125.9 (ArCH), 126.2 (ArCH), 126.9 (ArCH), 127.5
(ArCH), 128.5 (ArCH), 128.6 (ArCH), 130.2 (PhCH=CH + PhCH=CH), 134.2 (PhCH=CH),
137.0 (ArC), 137.7 (ArC), 174.2 (CO); m/z (ESI+) 375.4 ([M+H]+, 100%); HRMS (ESI+)
found 397.2128, expect 397.2144 for C26H30O2Na.
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S41
Crystal data and Structure Refinements
Figure S1 Crystal Structure of 2b (CCDC 1009956)
Table S1 Crystal data and structure refinement for 2b (CCDC 1009956)
Empirical formula C26H34O2
Formula weight 378.53
Temperature/K 566(2)
Crystal system orthorhombic
Space group Pca21
a/Å 13.7848(12)
b/Å 12.024(2)
c/Å 12.7279(13)
α/° 90
β/° 90
γ/° 90
Volume/Å3 2109.7(5)
Z 4
ρcalcmg/mm3 1.192
μ/mm-1
0.073
F(000) 824.0
2Θ range for data collection 6.402 to 50.052°
Index ranges -9 ≤ h ≤ 16, -14 ≤ k ≤ 5, -15 ≤ l ≤ 14
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S42
Reflections collected 4485
Independent reflections 3103[R(int) = 0.0732]
Data/restraints/parameters 3103/1/257
Goodness-of-fit on F2 1.043
Final R indexes [I>=2σ (I)] R1 = 0.0906, wR2 = 0.1778
Final R indexes [all data] R1 = 0.1502, wR2 = 0.2192
Largest diff. peak/hole / e Å-3
0.25/-0.25
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S43
Figure S2 Crystal Structure of 2d (CCDC 1012766)
Table S2 Crystal data and structure refinement for 2d (CCDC 1012766)
Empirical formula C26 H33 Br O2
Formula weight 457.43
Temperature 100(2) K
Wavelength 1.54178 Å
Crystal system Triclinic
Space group P-1
Unit cell dimensions a = 11.0845(3) Å
b = 12.9326(3) Å
c = 15.6251(4) Å
Volume 2210.80(10) Å3
Z 4
Density (calculated) 1.374 Mg/m3
Absorption coefficient 2.672 mm-1
F(000) 960
Crystal size 0.19 x 0.15 x 0.07 mm3
Theta range for data collection 3.43 to 72.15°.
Index ranges -13<=h<=12, -15<=k<=15, -19<=l<=19
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S44
Reflections collected 19984
Independent reflections 8306 [R(int) = 0.0292]
Completeness to theta = 67.00° 96.3 %
Absorption correction Semi-empirical from equivalents
Max. and min. transmission 0.8350 and 0.712437
Refinement method Full-matrix least-squares on F2
Data / restraints / parameters 8306 / 0 / 529
Goodness-of-fit on F2 1.046
Final R indices [I>2sigma(I)] R1 = 0.0329, wR2 = 0.0829
R indices (all data) R1 = 0.0368, wR2 = 0.0855
Largest diff. peak and hole 0.512 and -0.551 e.Å-3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S45
References
1 M. Szostak, M. Spain and D. J. Procter, J. Org. Chem., 2012, 77, 3049.
2 D. Parmar, H. Matsubara, K. Price, M. Spain and D. J. Procter, J. Am. Chem. Soc., 2012,
134, 12751.
3 N. Nazef, R. D. M. Davies and M. F. Greaney, Org. Lett., 2012, 14, 3720.
4 D. M. Barber, H. J. Sanganee and D. J. Dixon, Org. Lett., 2012, 14, 5290.
5 D. Parmar, K. Price, M. Spain, H. Matsubara, P. Bradley, D. J. Procter, J. Am. Chem. Soc.,
2011, 133, 2418.
6 R. Matsubara and T. F. Jamison, J. Am. Chem. Soc., 2010, 132, 6880.
7 A. Han, T. Spataru, J. Hartung, G. Li, and J. R. Norton, J. Org. Chem., 2014, 79, 1938.
1H and
13C NMR spectra
Ethyl 2-(2-(2-methyl-1,3-dioxolan-2-yl)ethyl)hept-6-enoate – S2
2013-08-05-DJP-33.010.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-06-25-DJP-46.020.esp
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
400 MHz, CDCl3
100 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S47
Ethyl 2-(3-oxobutyl)hept-6-enoate – S3
2013-11-27-DJP-50.010.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2013-11-27-DJP-50.013.esp
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
Chemical Shift (ppm)
400 MHz, CDCl3
100 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S48
(3R,6S)-6-Methyl-3-(pent-4-en-1-yl)-6-(1-phenylpropa-1,2-dien-1-yl)tetrahydro-2H-pyran-
2-one – trans-1a
2014-06-19-djp-40.020.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-06-22-djp-55.010.001.1r.esp
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
Chemical Shift (ppm)
400 MHz, CDCl3
100 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S49
(3S,6S)-6-Methyl-3-(pent-4-en-1-yl)-6-(1-phenylpropa-1,2-dien-1-yl)tetrahydro-2H-pyran-
2-one – cis-1a
2014-06-13-djp-19.010.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-06-16-djp-5.010.001.1r.esp
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
Chemical Shift (ppm)
500 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S50
(4S,4aS,5S,6S,7R,9aS)-4,5,7-Trimethyl-6-phenyldecahydro-4aH-benzo[7]annulene-4a,7-
diol - 2a
2013-02-05-Administrator-10.010.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2013-02-05-Administrator-10.011.001.1r.esp
160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
400 MHz, CDCl3
100 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S51
(1S,2R,3R,4S,5R)-1,3-Dimethyl-5-(pent-4-en-1-yl)-2-phenylcycloheptane-1,4-diol -3a
2013-02-05-djp-49.010.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-06-21-djp-55.010.001.1r.esp
144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
125 MHz, CDCl3
500 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S52
(E)-Ethyl 2-(3-oxobutyl)-7-phenylhept-6-enoate – S5
2013-05-24-djp-41.010.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2013-05-24-djp-41.013.001.1r.esp
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
Chemical Shift (ppm)
400 MHz, CDCl3
100 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S53
(3R,6S)-6-Methyl-3-((E)-5-phenylpent-4-en-1-yl)-6-(1-phenylpropa-1,2-dien-1-
yl)tetrahydro-2H-pyran-2-one – trans-1b
2013-07-18-djp-50.010.001.1r.esp
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2013-08-21-djp-48.010.001.1r.esp
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
Chemical Shift (ppm)
500 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S54
(1S,2R,3R,4S,5R)-1,3-Dimethyl-2-phenyl-5-((E)-5-phenylpent-4-en-1-yl)cycloheptane-1,4-
diol – 4b
2013-08-21-djp-50.011.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2013-08-21-djp-50.010.001.1r.esp
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
Chemical Shift (ppm)
500 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S55
(4R,4aR,5S,6S,7R,9aS)-4-Benzyl-5,7-dimethyl-6-phenyldecahydro-1H-benzo[7]annulene-
4a,7-diol – 2b
2013-09-11-djp-40.010.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2013-09-13-Administrator-58.011.001.1r.esp
152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
500 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S56
(4S,4aS,5R,6R,7S,9aR)-7-Methyl-5-(methyl-d)-6-phenyl-4-((S)-phenylmethyl-d)decahydro-
4aH-benzo[7]annulene-5,6-d2-4a,7-diol-d2 – 2b-D4
2014-06-19-djp-60.010.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-06-21-djp-56.010.001.1r.esp
144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
400 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S57
Ethyl (E)-2-(3-oxobutyl)-7-(4-(trifluoromethyl)phenyl)hept-6-enoate – S6
2014-03-13-djp-27.010.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5
Chemical Shift (ppm)
2014-06-05-staff-5.010.001.1r.esp
208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
500 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S58
(3R,6S)-6-Methyl-6-(1-phenyl-propa-1,2-dien-1-yl)-3-((E)-5-(4-
(trifluoromethyl)phenyl)pent-4-en-1-yl)tetrahydro-2H-pyran-2-one – trans-1c
2014-01-28-staff-10.010.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-03-20-staff-28.012.001.1r.esp
208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
500 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S59
(4S,4aS,5R,6R,7S,9aR)-5,7-Dimethyl-6-phenyl-4-(4-(trifluoromethyl)benzyl)decahydro-
4aH-benzo[7]annulene-4a,7-diol – 2c
2014-06-16-djp-55.020.001.1r.esp
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-06-16-djp-55.021.001.1r.esp
168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
500 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S60
Ethyl (E)-7-(4-bromophenyl)-2-(3-oxobutyl)hept-6-enoate – S7
400 MHz, CDCl3
100 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S61
rac-(3R,6S)-3-((E)-5-(4-Bromophenyl)pent-4-en-1-yl)-6-methyl-6-(1-phenyl-2l5-propa-1,2-
dien-1-yl)tetrahydro-2H-pyran-2-one – trans-1d
2014-07-08-DJP-6.010.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-07-08-djp-6.011.001.1r.esp
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
Chemical Shift (ppm)
125 MHz, CDCl3
500 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S62
(4S,4aS,5R,6R,7S,9aR)-4-(4-Bromobenzyl)-5,7-dimethyl-6-phenyldecahydro-4aH-
benzo[7]annulene-4a,7-diol – 2d
2014-03-10-djp-20.020.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-03-10-DJP-20.021.esp
152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
500 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S63
Ethyl (E)-2-(3-oxobutyl)-7-(p-tolyl)hept-6-enoate – S8
2014-07-02-djp-6.010.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-07-02-djp-6.011.001.1r.esp
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
Chemical Shift (ppm)
125 MHz, CDCl3
500 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S64
rac-(3R,6S)-6-Methyl-6-(1-phenyl-propa-1,2-dien-1-yl)-3-((E)-5-(p-tolyl)pent-4-en-1-
yl)tetrahydro-2H-pyran-2-one – trans-1e
2014-05-01-DJP-14.010.esp
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-07-04-djp-34.011.001.1r.esp
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
Chemical Shift (ppm)
400 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S65
(4S,4aS,5R,6R,7S,9aR)-5,7-Dimethyl-4-(4-methylbenzyl)-6-phenyldecahydro-4aH-
benzo[7]annulene-4a,7-diol – 2e
2014-06-19-DJP-42.010.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-06-21-djp-54_2.010.001.1r.esp
144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
400 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S66
Ethyl (E)-7-(2-chlorophenyl)-2-(3-oxobutyl)hept-6-enoate – S9
2014-07-02-djp-7.010.001.1r.esp
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-07-04-djp-37.010.001.1r.esp
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
Chemical Shift (ppm)
500 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S67
rac-(3R,6S)-3-((E)-5-(2-Chlorophenyl)pent-4-en-1-yl)-6-methyl-6-(1-phenyl-propa-1,2-
dien-1-yl)tetrahydro-2H-pyran-2-one – trans-1f
2014-03-20-staff-27.010.001.1r.esp
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-03-20-staff-27.012.001.1r.esp
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
Chemical Shift (ppm)
125 MHz, CDCl3
500 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S68
rac-(4S,4aS,5R,6R,7S,9aR)-4-(2-Chlorobenzyl)-5,7-dimethyl-6-phenyldecahydro-4aH-
benzo[7]annulene-4a,7-diol – 2f
2014-06-25-djp-48.014.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-06-25-djp-48.011.esp
160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
500 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S69
ethyl (E)-4,4-dimethylhepta-2,6-dienoate – S10
2014-05-05-djp-18.010.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-05-05-djp-18.011.001.1r.esp
200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
400 MHz, CDCl3
100 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S70
methyl (E)-4,4-dimethyl-7-phenylhept-6-enoate – S12
2014-06-25-djp-47.010.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-06-25-djp-47.011.esp
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
400 MHz, CDCl3
100 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S71
ethyl (E)-4,4-dimethyl-2-(2-(2-methyl-1,3-dioxolan-2-yl)ethyl)-7-phenylhept-6-enoate – S14
2014-05-30-djp-14.010.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-05-30-djp-14.011.001.1r.esp
184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Chemical Shift (ppm)
500 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S72
methyl (E)-4,4-dimethyl-2-(3-oxobutyl)-7-phenylhept-6-enoate – S15
2014-05-31-djp-17.010.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-05-31-djp-17.011.001.1r.esp
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
Chemical Shift (ppm)
500 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S73
(3S,6S)-3-((E)-2,2-dimethyl-5-phenylpent-4-en-1-yl)-6-methyl-6-(1-phenyl-2l5-propa-1,2-
dien-1-yl)tetrahydro-2H-pyran-2-one – trans-1g
2014-06-08-djp-40.010.001.1r.esp
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
2014-06-25-staff-50.012.esp
216 208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8
Chemical Shift (ppm)
500 MHz, CDCl3
125 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S74
Ethyl 2-(3-oxobutyl)-7-phenylhept-6-ynoate – S18
100 MHz, CDCl3
400 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S75
(3R,6S)-6-(1-(Dimethyl(phenyl)silyl)--propa-1,2-dien-1-yl)-6-methyl-3-(5-phenylpent-4-yn-
1-yl)tetrahydro-2H-pyran-2-one trans-1h
400 MHz, CDCl3
100 MHz, CDCl3
SmI2–H2O-mediated 5-exo/6-exo lactone radical cyclisation cascades Yalavac et al.
S76
(3R,6S)-6-Cinnamyl-6-methyl-3-(5-phenylpent-4-en-1-yl)tetrahydro-2H-pyran-2-one -
trans-1i
400 MHz, CDCl3
100 MHz, CDCl3